Pain
Everything in the library studied for it, medical and holistic together. Within each kind, what was shown to help comes first, strongest evidence first. What was tested and not shown to help stays on the list.
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Medication
Knee and hip osteoarthritis pain
Shown to lower knee and hip osteoarthritis pain by about 3 points on a 100-point scale, below the 9 points the reviewers set as clinically important.
The numbers and sources
- Effect
- In 10 placebo-controlled trials, pain fell 23 points on a 0 to 100 scale on placebo and 3.23 points more on paracetamol (95% CI 1.02 to 5.43), against a minimal clinically important difference of 9. Physical function improved 2.9 points more than on placebo (95% CI 0.95 to 4.89). Effects did not differ between 3.0 g a day or less and 3.9 g or more [8]. An earlier meta-analysis found a similar effect on pain (-3.7 points, 95% CI -5.5 to -1.9) and disability (-2.9, 95% CI -4.9 to -0.9) [9]. An overview of systematic reviews put the pain effect at 0.3 points on a 0 to 10 scale (95% CI 0.1 to 0.6) [5].
- Population
- 3,541 people with hip or knee osteoarthritis in 10 trials at 1.95 to 4 g a day, most followed for 3 months [8]; 13 randomized trials in spinal pain and osteoarthritis [9].
- Sources
- [8], [9], [5]
- Caveats
- The reviews share trials and authors. No trial reported quality of life [8].
Nerve pain after shingles
Shown to give at least 50% pain relief to about 32% of people with postherpetic neuralgia, against 13% to 17% on placebo.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- With gabapentin at 1,200 mg a day or more, 32% had substantial benefit against 17% on placebo (RR 1.8, 95% CI 1.5 to 2.1, number needed to treat 6.7), and 46% had moderate benefit against 25% (number needed to treat 4.8) [1]. With pregabalin 300 mg a day, 32% had at least 50% pain reduction against 13% on placebo (RR 2.5, 95% CI 1.9 to 3.4, number needed to treat 5.3). With 600 mg a day it was 41% against 15% (RR 2.7, 95% CI 2.0 to 3.5, number needed to treat 3.9) [2].
- Population
- 2,260 participants in 8 gabapentin studies of 4 to 12 weeks [1]; 713 and 732 participants in 4 pregabalin studies at each dose [2].
- Sources
- [1], [2]
- Caveats
- Both reviews rated the evidence moderate quality. Most people did not reach 50% relief on either drug.
Diabetic nerve pain
Shown to give at least 50% pain relief to 38% on gabapentin against 21% on placebo, and to 31% on pregabalin 300 mg against 24%.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- With gabapentin at 1,200 mg a day or more, 38% had substantial benefit against 21% on placebo (RR 1.9, 95% CI 1.5 to 2.3, number needed to treat 5.9), and 52% had moderate benefit against 37% (number needed to treat 6.6) [1]. With pregabalin 300 mg a day, 31% had at least 50% pain reduction against 24% on placebo (RR 1.3, 95% CI 1.2 to 1.5), and 47% had at least 30% reduction against 42% (number needed to treat 22). With 600 mg a day, 41% had at least 50% reduction against 28% (RR 1.4, 95% CI 1.2 to 1.7, number needed to treat 7.8) [2].
- Population
- 1,277 participants in 6 gabapentin studies [1]; 2,931 participants in 11 studies of pregabalin 300 mg and 1,015 in 5 studies of 600 mg [2].
- Sources
- [1], [2]
- Caveats
- Gabapentin is not FDA-approved for diabetic nerve pain. The pregabalin effect at 300 mg was small, and the 600 mg evidence was rated low quality. The review found an absence of efficacy for pregabalin in HIV neuropathy [2].
Acute low back pain
Shown to lower acute low back pain by about 8 points on a 100-point scale within 2 weeks, with no gain in disability and more side effects.
The numbers and sources
- Effect
- In acute low back pain, non-benzodiazepine muscle relaxants lowered pain intensity at 2 weeks or less by 7.7 points on a 0 to 100 scale against control (95% CI 3.3 to 12.1), with no significant change in disability (-3.3, 95% CI -7.3 to 0.7). Adverse events were more frequent (RR 1.6, 95% CI 1.2 to 2.0) [1]. An earlier Cochrane review found non-benzodiazepine relaxants better than placebo for pain relief after 2 to 4 days (RR 0.80, 95% CI 0.71 to 0.89) and global efficacy (RR 0.49, 95% CI 0.25 to 0.95), with more adverse events (RR 1.50, 95% CI 1.14 to 1.98) [2]. For cyclobenzaprine, people were more likely to report improvement by day 14 than on placebo (OR 4.7, 95% CI 2.7 to 8.1), a number needed to treat of 2.7, with effect sizes of 0.38 to 0.58 that were largest in the first 4 days [3].
- Population
- 6,505 adults with non-specific low back pain in 31 pooled trials, from 49 reviewed [1]; 30 trials, 24 of them in acute low back pain [2]; randomized placebo-controlled trials of cyclobenzaprine in adults with back pain [3].
- Sources
- [1], [2], [3]
- Caveats
- The most recent review rated its evidence very low certainty and described the pain reduction as not clinically important, with most trials at high risk of bias [1]. A separate review found fair evidence for cyclobenzaprine and tizanidine in acute back or neck pain and very limited or inconsistent data for methocarbamol and baclofen [4].
Joint pain in knee or hip osteoarthritis
Shown to ease knee osteoarthritis pain and stiffness over placebo, including topical diclofenac. Pain relief was similar to exercise therapy.
The numbers and sources
- Effect
- Pain relief did not differ between exercise therapy and oral NSAIDs or paracetamol at about 4 weeks (SMD -0.12, 95% CrI -1.74 to 1.50), 8 weeks or 24 weeks. Function also did not differ at any time point [2]. Against placebo in knee osteoarthritis, etoricoxib improved WOMAC pain (MD -0.44, 95% CI -0.61 to -0.26), naproxen WOMAC function (MD -0.43, 95% CI -0.82 to -0.04) and diclofenac WOMAC stiffness (MD -0.40, 95% CI -0.67 to -0.13) [3]. Topical diclofenac gel, solution and patch each lowered knee pain and improved function against placebo. The patch gave the largest relief at 1 to 2 weeks (SMD -0.64, 95% CI -0.90 to -0.39), and skin and whole-body side effects stayed low [4].
- Population
- 152 RCTs with 17,431 people with knee or hip osteoarthritis [2]; 31 RCTs with 68,539 people with knee osteoarthritis comparing 16 treatments [3]; 12 RCTs of topical diclofenac in knee osteoarthritis [4].
- Sources
- [2], [3], [4]
- Caveats
- The comparison with exercise is mostly indirect, and NSAIDs were pooled with paracetamol. Few trials reported 8- and 24-week results [2]. The network estimates in [3] compare drugs indirectly. [4] covered up to 12 weeks.
Period pain
Shown to relieve period pain more than placebo, with moderate or excellent relief in 45% to 53% of women against 18% on placebo.
Compared with placebo [24][25]; paracetamol [24]; other NSAIDs and aspirin [24][25]
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In primary dysmenorrhea, NSAIDs gave more pain relief than placebo (OR 4.37, 95% CI 3.76 to 5.09, 35 RCTs, low-quality evidence). If 18% of women on placebo got moderate or excellent relief, 45% to 53% on NSAIDs would. NSAIDs also relieved pain more than paracetamol (OR 1.89, 95% CI 1.05 to 3.43, 3 RCTs). No single NSAID was shown to relieve pain more or cause fewer side effects than another [24]. A network meta-analysis of 13 drugs found most gave more pain relief than aspirin, and ketoprofen, naproxen, rofecoxib and ibuprofen scored higher than placebo on overall assessment [25].
- Population
- 80 RCTs with 5,820 women with primary dysmenorrhea, comparing 20 NSAIDs [24]; 72 RCTs with 5,723 patients [25].
- Sources
- [24], [25]
- Caveats
- The Cochrane authors rated most evidence low quality because study methods were poorly reported. 59% of trials were commercially funded and 31% did not state funding [24].
Chronic pain not caused by cancer
Shown to lower chronic non-cancer pain by about 0.7 points on a 10-point scale against placebo, with no advantage found over non-opioid drugs.
The numbers and sources
- Effect
- Across 96 trials, opioids lowered pain against placebo by 0.69 cm on a 10 cm scale (95% CI 0.56 to 0.82) and improved physical function by 2.04 points on a 100-point scale (95% CI 1.41 to 2.68). The modeled share reaching a minimally important pain difference was 11.9 percentage points higher. Pain relief was similar to that with NSAIDs (difference -0.60 cm, 95% CI -1.54 to 0.34) and tricyclic antidepressants (-0.13 cm, 95% CI -0.99 to 0.74) [6]. A federal evidence review of 115 trials also found small short-term benefits against placebo in pain, function and sleep, smaller at 3 to 6 months than at 1 to 3 months, and no difference from non-opioid drugs. It found no trial that evaluated intermediate or long-term benefits against placebo [7]. Over 12 months in veterans with chronic back pain or hip or knee osteoarthritis pain, pain-related function did not differ between opioid and non-opioid treatment (3.4 against 3.3), and pain intensity was lower in the non-opioid group (4.0 against 3.5) [8].
- Population
- 26,169 participants in 96 trials, median age 58 [6]; 115 randomized trials and 40 observational studies [7]; 240 veterans randomized to opioid or non-opioid treatment strategies [8].
- Sources
- [6], [7], [8]
- Caveats
- Most placebo-controlled trials were short. The 12-month trial was pragmatic, with only the outcome assessment masked [8].
Knee and hip osteoarthritis pain
Shown to lower knee and hip osteoarthritis pain by small amounts against placebo, about 0.7 points of 10 for oxycodone-type opioids and 4% for tramadol.
The numbers and sources
- Effect
- In 22 trials, 10 of them of oral oxycodone, opioids lowered pain by 0.7 cm on a 10 cm scale against placebo (SMD -0.28, 95% CI -0.35 to -0.20), a number needed to treat of 10, and improved function by 0.6 units on a 0 to 10 scale. Effects were larger in trials of 4 weeks or less. Dropouts over adverse events were 6.4% against 1.7% [9]. In 22 trials of tramadol, pain improved 4% more than on placebo (95% CI 3% to 5%), and 15 of 100 against 10 of 100 improved by 20%. Physical function improved 4% more (95% CI 2% to 6%). The authors judged neither an important benefit [10].
- Population
- 8,275 people with knee or hip osteoarthritis in 22 trials [9]; 22 trials with 3,871 participants randomized to tramadol alone or with acetaminophen and 2,625 to placebo or an active control, mean duration 2 months [10].
- Sources
- [9], [10]
- Caveats
- Most tramadol trials were funded by industry, and 10 of 22 had incomplete outcome data [10]. The first review found signs of small-study bias [9].
Endometriosis pain, compared with placebo
Shown to ease pain in women with endometriosis against placebo, by 2.58 points on a visual analogue pain scale for oral progestins in pooled trials.
Compared with placebo or no treatment, pooled together [5]; placebo [6][7][8]
The numbers and sources
- Effect
- Against placebo or no treatment, oral progestins lowered overall pain at six months (MD -2.58, 95% CI -3.13 to -2.03, moderate certainty) and period pain at three months (RR 0.21, 95% CI 0.07 to 0.70), while pelvic pain at three months did not differ (RR 0.7, 95% CI 0.29 to 1.69). Quality of life rose (SF-36 MD 4.11, 95% CI 2.41 to 5.82, high certainty) [5]. A network meta-analysis found dienogest superior to placebo for pelvic pain outside periods and for pain during sex [6]. In a 12-week placebo-controlled trial, pain on a 100 mm scale fell 27.4 mm with dienogest 2 mg and 15.1 mm with placebo, a difference of 12.3 mm [7]. In a 24-week trial in China, the difference was 24.54 mm (95% CI 19.15 to 29.93) [8].
- Population
- 8 trials of oral progestins against placebo or no treatment, within a review of 33 trials and 5,059 women with endometriosis confirmed at laparoscopy [5]. 3,259 women in 8 trials [6]. 198 women aged 18 to 45 in Germany, Italy and Ukraine [7]. 255 Chinese women aged 18 to 45 [8].
- Sources
- [5], [6], [7], [8]
- Caveats
- The Cochrane comparison pools placebo and no-treatment arms, so it mixes a blinded comparison with an unblinded one [5]. Pain fell 15.1 mm on placebo alone in the 12-week trial [7]. The review notes that few trials report each outcome [5].
Diabetic nerve pain
Shown to cut pain by half or more in painful diabetic neuropathy on duloxetine 60 mg, with about 5 treated for one extra person helped.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- The evidence is for duloxetine. At 60 mg a day, a 50% or greater drop in pain at 12 weeks was more likely than on placebo (RR 1.73, 95% CI 1.44 to 2.08), a number needed to treat of 5 (95% CI 4 to 7). Doses of 60 and 120 mg both reduced pain, and lower doses did not. 16% of participants stopped the drug for adverse effects [13]. Across neuropathic pain conditions, the combined number needed to treat for SNRIs was 6.4 (95% CI 5.2 to 8.4), with duloxetine making up 9 of 14 studies [14]. In a network meta-analysis of chronic pain, duloxetine was the highest-ranked antidepressant, and 60 mg did as well as higher doses on most outcomes [15].
- Population
- 2,728 participants with painful diabetic neuropathy in 8 studies [13]; 229 studies of drugs for neuropathic pain in adults [14]; 28,664 adults with chronic pain in 176 studies averaging 10 weeks [15].
- Sources
- [13], [14], [15]
- Caveats
- Almost every duloxetine study was run or sponsored by the manufacturer [13]. An analysis of publication bias suggested treatment effects in neuropathic pain were overstated by about 10% [14]. Most studies measured short-term outcomes only [15].
Fibromyalgia
Shown to raise the share with 50% pain relief in fibromyalgia from about 21% to 31%, a gain Cochrane reviewers judged not clinically relevant.
The numbers and sources
- How common
- Common: between 1 in 100 and 1 in 10 people.
- Effect
- On duloxetine or milnacipran, 31% reported pain relief of 50% or greater against 21% on placebo (risk difference 0.09, 95% CI 0.07 to 0.11), a number needed to treat of 11. More people rated themselves much or very much improved (52% vs 29%, number needed to treat 5). Fatigue changed little (SMD -0.13) [16]. For duloxetine 60 mg alone, the risk ratio for 50% pain relief was 1.57 (95% CI 1.20 to 2.06) at 12 weeks, a number needed to treat of 8 [13]. Across chronic pain conditions, with fibromyalgia the most studied, duloxetine 60 mg raised the odds of substantial pain relief (OR 1.91, 95% CI 1.69 to 2.17) [15].
- Population
- 7,903 participants in 18 studies, 7 of duloxetine, 9 of milnacipran and 1 of desvenlafaxine [16]; 2,249 participants with fibromyalgia in 6 studies [13]; 4,490 participants in 16 studies for the pain relief outcome [15].
- Sources
- [16], [13], [15]
- Caveats
- Evidence quality was rated low for all comparisons with placebo, over concerns about publication bias [16]. The pooled figures mix duloxetine with milnacipran, which is outside this page. The band above uses the 9 to 10 point gain in responders.
Acute pain after surgery
Shown to give at least half pain relief to about half of adults after surgery with one dose, against about 20% on placebo.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Across 51 trials, about half of participants given a single standard dose had at least 50% pain relief over 4 to 6 hours, against about 20% on placebo. The number needed to treat was 3.5 (95% CI 2.7 to 4.8) at 500 mg, 4.6 (3.9 to 5.5) at 600 to 650 mg and 3.6 (3.4 to 4.0) at 975 to 1,000 mg, with no dose response. About half needed more pain medication within 4 to 6 hours, against about 70% on placebo [1]. An overview of Cochrane reviews of over-the-counter pain relievers found paracetamol and aspirin had numbers needed to treat of 3 or above and success rates of 11% to 43%, and ibuprofen plus paracetamol combinations had numbers needed to treat below 2 [2].
- Population
- 5,762 adults in 51 single-dose trials, 3,277 given paracetamol and 2,425 placebo [1]; 10 Cochrane reviews covering 21 drugs, doses and formulations, mostly tested after third molar extraction [2].
- Sources
- [1], [2]
- Caveats
- Single doses followed for 4 to 6 hours. The overview draws on the same Cochrane review, so the two are not independent. Adverse event reporting in the trials was inconsistent and often incomplete [1].
Taken with ibuprofen for acute pain
Shown to give at least half pain relief to about 7 in 10 adults after surgery when taken with ibuprofen, against 7% on placebo.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- At least 50% of maximum pain relief over 6 hours was reached by 69% on ibuprofen 200 mg plus paracetamol 500 mg, 73% on ibuprofen 400 mg plus paracetamol 1,000 mg and 7% on placebo, giving numbers needed to treat of 1.6 and 1.5. On ibuprofen 400 mg alone the share was 52%. Median time to rescue medication was 7.6 and 8.3 hours on the combinations and 1.7 hours on placebo. One or more adverse events were reported by 30% and 29% on the combinations and 48% on placebo [3].
- Population
- 1,647 participants in 3 single-dose trials [3].
- Sources
- [3]
- Caveats
- Three trials of one dose each. No serious adverse events were reported [3].
Fibromyalgia
Shown in very low quality evidence to make at least 50% pain relief about three times as likely as placebo, with about 4 treated for one extra responder.
Compared with placebo and other active treatments [6]
The numbers and sources
- Effect
- Using third-tier evidence, at least 50% pain relief was more likely on amitriptyline than placebo (RR 3.0, 95% CI 1.7 to 4.9), a number needed to treat of 4.1. Fatigue, sleep, quality of life and tender points showed no consistent differences. At least one adverse event occurred in 78% on amitriptyline and 47% on placebo [6].
- Population
- 649 adults in nine studies of 6 to 24 weeks at 25 to 50 mg a day [6].
- Sources
- [6]
- Caveats
- No study had 50 or more participants per arm, and the review found no first or second tier evidence [6].
Paget's disease of bone
Shown to relieve bone pain in Paget's disease more often than placebo, 31% against 9%, with one zoledronic acid infusion normalizing alkaline phosphatase in 89% at 6 months.
Compared with placebo and other bisphosphonates [12]; risedronate [13]
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Bone pain disappeared in 31% on a bisphosphonate and 9% on placebo (RR 3.42, 95% CI 1.31 to 8.90), a number needed to treat of 5. Fractures did not clearly differ. Zoledronate relieved pain more often than pamidronate or risedronate in single trials [12]. In two 6-month trials, one 5 mg infusion of zoledronic acid normalized serum alkaline phosphatase in 89% against 58% on risedronate 30 mg daily for 2 months, and a therapeutic response was seen in 96% against 74% [13].
- Population
- 3,168 people in 20 trials, mean age 66 to 74, 51% to 74% men, mostly with raised alkaline phosphatase [12]; 349 adults with moderate to severe Paget's disease, mean age 70 [13].
- Sources
- [12], [13]
- Caveats
- Moderate-quality evidence for pain, and mean follow-up was 6 months [12]. Treating to normalize alkaline phosphatase did not improve pain or quality of life over treating symptoms [12].
Fibromyalgia
Shown to give at least 50% pain relief to about 22% to 24% of people with fibromyalgia on pregabalin, against about 14% on placebo.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- With pregabalin 300 to 600 mg a day, about 22% to 24% had at least 50% pain reduction after 12 or 13 weeks against about 14% on placebo, and 39% to 43% had at least 30% reduction against about 28%. Numbers needed to treat ranged from 7 to 14 [3]. For gabapentin, one 12-week trial found at least 30% pain reduction in 49% (38 of 75) against 31% (23 of 75) on placebo, and the reviewers judged the evidence insufficient to support or refute a benefit [4].
- Population
- 3,283 participants in 5 pregabalin trials of 8 to 13 weeks [3]; 150 participants in one gabapentin trial [4].
- Sources
- [3], [4]
- Caveats
- The evidence is for pregabalin, rated high quality. The gabapentin trial was rated very low quality, and gabapentin is not approved for fibromyalgia. About 9 in 100 people gained substantial benefit beyond placebo.
Period pain
Shown to reduce period pain in women more than placebo, with improvement in 37% to 60% against 28%, along with more irregular bleeding, headache and nausea.
Compared with placebo or no treatment [5]
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Combined pills reduced pain more than placebo (SMD -0.58, 95% CI -0.74 to -0.41, high quality) and raised the chance of improvement (RR 1.65), from 28% to between 37% and 60%. Extra medication and missed work fell (RR 0.63 each). Continuous pill use may reduce pain more than the standard regimen [5].
- Population
- 3,723 women in 21 trials [5].
- Sources
- [5]
- Caveats
- The dichotomous pain result was low quality [5].
Endometriosis pain (combined pill)
Shown to ease endometriosis period pain more than placebo in two small trials, in very low-quality evidence. Pain at 6 months matched goserelin in one trial.
Compared with placebo [32][33]; goserelin [32]; oral progestins and GnRH agonists [33]
The numbers and sources
- Effect
- Against placebo, combined pills lowered period pain on a visual analogue scale (MD -23.68 points, 95% CI -28.75 to -18.62, 2 RCTs, 327 women) and on a 0 to 3 verbal scale (MD -1.30, 95% CI -1.84 to -0.76, 1 RCT, 96 women). At 6 months, pain did not differ from goserelin (MD -0.10 on a 1 to 10 scale, 95% CI -1.28 to 1.08, 50 women) [32]. A review of 9 RCTs and 9 observational studies found combined hormonal contraceptives lowered period pain, pelvic pain and pain with sex from baseline in most studies, about as much as or less than oral progestins and GnRH agonists [33].
- Population
- 612 women with surgically confirmed endometriosis in 5 trials, 404 analyzed [32]; women with endometriosis in 18 studies [33].
- Sources
- [32], [33]
- Caveats
- Both placebo trials were at high risk of bias, with substantial involvement of the drug company that funded them [32]. Only 2 of the 9 trials in [33] were placebo-controlled, and most were not blinded.
Pain after surgery
Shown to cut pain after surgery by about 19% and opioid use by about 8 mg morphine over 24 hours, when given around the operation.
Compared with placebo, or a basic pain reliever alone [10]
The numbers and sources
- Effect
- Perioperative intravenous ketamine reduced opioid use over 24 hours by 8 mg morphine equivalents (19% of 42 mg on placebo) and over 48 hours by 13 mg. Pain at rest fell 5 points on a 100 mm scale at 24 hours (19% lower) and 48 hours, and pain on movement 6 points. Time to first pain relief request lengthened by 54 minutes. Nausea and vomiting fell from 27% to 23% [10].
- Population
- 8,341 adults in 130 trials across many operations [10].
- Sources
- [10]
- Caveats
- Most trials had fewer than 50 people per arm, with small-study effects. No analysis by dose was possible [10].
Chronic pain
Shown to lower chronic pain scores by about 1.8 points on a 10-point scale for up to 2 weeks after an infusion, with 51% responding against 19%.
Compared with placebo infusions [11]
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Up to 2 weeks after an infusion, pain scores fell 1.83 points more than placebo on a 0 to 10 scale (95% CI 1.31 to 2.35). In 3 studies reporting responders, 51.3% on ketamine and 19.4% on placebo responded (RR 2.43, 95% CI 1.10 to 5.40) [11].
- Population
- 211 patients with neuropathic, mixed or other chronic pain in 7 trials [11].
- Sources
- [11]
- Caveats
- All but one trial had high risk of bias, and follow-up was short [11].
Fibromyalgia
Shown to improve overall fibromyalgia symptoms with cyclobenzaprine, with about 5 treated for one extra person improved, and no change in fatigue or tender points.
The numbers and sources
- Effect
- Across 5 placebo-controlled trials, people on cyclobenzaprine were more likely to report overall improvement (OR 3.0, 95% CI 1.6 to 5.6), a risk difference of 0.21 (95% CI 0.09 to 0.34) and a number needed to treat of 4.8 (95% CI 3.0 to 11). Pain improved early in treatment and sleep improved. Fatigue and tender points did not improve at any time [9].
- Population
- People with fibromyalgia in 5 randomized, placebo-controlled trials of cyclobenzaprine [9].
- Sources
- [9]
- Caveats
- One meta-analysis of 5 trials, of cyclobenzaprine only. Not an FDA-approved use [10].
Low back pain
Shown to lower acute low back pain slightly with diclofenac, with other NSAIDs unconfirmed or showing no benefit.
The numbers and sources
- Effect
- Against placebo, diclofenac lowered pain intensity in acute low back pain. Ibuprofen in acute low back pain without nerve root pain and naproxen in acute low back pain with nerve root pain showed results the authors rated as needing confirmation. Celecoxib, etoricoxib and ketoprofen showed no evidence of benefit. The authors judged every effect small [5].
- Population
- 11 RCTs with 3,784 people, 1,642 with acute and 2,142 with chronic low back pain [5].
- Sources
- [5]
- Caveats
- 5 of the 11 trials were at high risk of bias for pain, and more than half used the NSAID as a comparator for another treatment [5].
Acute pain after surgery
Shown to relieve pain after surgery in single doses, with about 3 adults given oxycodone 10 mg plus acetaminophen for one extra with half pain relief.
The numbers and sources
- Effect
- For at least 50% pain relief after surgery, the number needed to treat against placebo was 4.6 (95% CI 2.9 to 11) for oxycodone 15 mg alone and 2.7 (2.4 to 3.1) for oxycodone 10 mg plus paracetamol 650 mg, with a dose response for the combination. Relief lasted 10 hours at that combination dose and 4 hours at half of it. Adverse events were more frequent than on placebo [1]. In individual patient data from 18 single-dose trials, tramadol 50, 100 and 150 mg had numbers needed to treat of 7.1 (4.6 to 18), 4.8 (3.4 to 8.2) and 2.4 (2.0 to 3.1) in pain after surgery, with more adverse events at higher doses [2].
- Population
- 2,641 adults in 20 studies of oxycodone [1]; 3,453 patients with moderate or severe pain after surgery or dental extraction in 18 trials of tramadol [2].
- Sources
- [1], [2]
- Caveats
- Single doses followed for hours. The evidence here is for oxycodone and tramadol.
Nerve pain
Shown to give at least half pain relief to 53% on tramadol against 30% on placebo in small nerve pain trials the reviewers rated low quality.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- In 3 studies, 53% on tramadol and 30% on placebo had at least 50% pain relief (RR 2.2, 95% CI 1.02 to 4.6), a number needed to treat of 4.4. Any adverse event was reported by 58% against 34%, and 16% against 3% withdrew over adverse events [11]. In 3 studies in painful diabetic neuropathy, at least moderate benefit was reported by 44% on modified-release oxycodone and 27% on placebo (number needed to treat 5.7). Any adverse event was reported by 86% against 63% [12].
- Population
- 438 adults with neuropathic pain for at least 3 months in 6 studies of tramadol lasting 4 to 6 weeks [11]; 687 adults in 5 studies of oxycodone, 637 with painful diabetic neuropathy and 50 with postherpetic neuralgia [12].
- Sources
- [11], [12]
- Caveats
- The reviewers rated the tramadol evidence low quality and the oxycodone evidence very low quality, citing small studies, short duration and risk of bias. No oxycodone study reported at least 50% pain relief [12].
Sciatica and low back pain
Shown to improve function slightly in sciatica from a herniated disk, with pain about half a point of 10 lower and no change in surgery rates.
The numbers and sources
- Effect
- In adults with sciatica from a herniated disk, a 15-day prednisone course improved disability at 3 weeks by 6.4 points more than placebo on a 100-point scale (95% CI 1.9 to 10.9) and by 7.4 points at 52 weeks. Leg pain did not differ at 3 weeks (0.3 points of 10, 95% CI -0.4 to 1.0) or 52 weeks, and surgery rates did not differ [9]. A Cochrane review of 13 trials found systemic corticosteroids probably lower radicular pain slightly in the short term (0.56 points of 10, 95% CI 0.04 to 1.08) and raise the likelihood of improved function (RR 1.52, 95% CI 1.22 to 1.91), with no difference in surgery (RR 1.00, 95% CI 0.68 to 1.47). For low back pain without sciatica and for spinal stenosis, the limited evidence showed no clear benefit [10].
- Population
- 269 adults with radicular pain for 3 months or less and a herniated disk on MRI, 181 on prednisone and 88 on placebo [9]; 1,047 participants in 13 trials [10].
- Sources
- [9], [10]
- Caveats
- The long-term function result rests on a single trial [10]. At least one adverse event was reported by 49.2% on prednisone and 23.9% on placebo at 3 weeks [9].
Sore throat
Shown to raise the share with sore throat pain relieved at 24 hours by 12 percentage points after one low dose, mostly of dexamethasone.
The numbers and sources
- Effect
- After a single low dose, most often oral dexamethasone at up to 10 mg, people were about twice as likely to have pain relief at 24 hours (RR 2.2, 95% CI 1.2 to 4.3, risk difference 12.4%) and 1.5 times as likely to have no pain at 48 hours (RR 1.5, 95% CI 1.3 to 1.8, risk difference 18.3%). Pain relief began 4.8 hours earlier on average. Six of the 9 trials that looked for adverse events reported none [11].
- Population
- 1,426 people with sore throat in 10 trials [11].
- Sources
- [11]
- Caveats
- The trials gave one dose and did not assess repeated courses [11].
Endometriosis pain, compared with GnRH agonist injections
Shown to ease endometriosis pain in women about as much as GnRH agonist injections such as leuprolide, with less bone loss and fewer hot flushes.
Compared with GnRH agonists [5]; leuprolide injections [9][10][11][1]; a GnRH antagonist [5]
The numbers and sources
- Effect
- Oral progestins and GnRH agonists did not differ for overall pain (MD -0.01, 95% CI -0.30 to 0.28, low certainty), and side effects overall were more frequent with oral progestins (RR 1.44, 95% CI 1.11 to 1.86). Depot progestins reduced period pain slightly more than GnRH agonists (RR 0.93, 95% CI 0.89 to 0.97, high certainty) with fewer side effects overall (RR 0.03, 95% CI 0.01 to 0.11). Against a GnRH antagonist, more women stopped a depot progestin for side effects (RR 2.02, 95% CI 1.04 to 3.94) [5]. Over 24 weeks, pain fell 47.5 mm with dienogest and 46.0 mm with leuprolide, and spine bone density changed +0.25% against -4.04% [9]. The medroxyprogesterone injection matched leuprolide on four of five pain signs at 6 months and all five at 18 months, with less bone loss [10][11]. Moderate or severe hot flushes at month 6 were reported by 27% on the injection and 69% on leuprolide [1].
- Population
- 10 trials of oral progestins and 2 of depot progestins against GnRH agonists [5]. 252 women [9]. 274 women in Canada and the US [10]. 300 women [11]. Women in the injection's two endometriosis trials [1].
- Sources
- [5], [9], [10], [11], [1]
- Caveats
- These are equivalence comparisons between two active drugs, not against placebo. The dienogest trial was open-label [9], and the injection trials blinded only the evaluator [10][11].
Chronic back pain and osteoarthritis pain
Shown to lower back pain by about 5 points on a 100-point scale, which reviewers called not clinically important, and osteoarthritis pain by about 10 points.
The numbers and sources
- Effect
- On a scale from 0 to 100, SNRIs lowered back pain by 5.30 points more than placebo at 3 to 13 weeks (95% CI 3.30 to 7.31) and osteoarthritis pain by 9.72 points (95% CI 6.69 to 12.75). Back pain disability fell by 3.55 points. The authors judged the back pain effect small and not clinically important, and could not exclude a clinically important effect in osteoarthritis [17]. Across chronic pain conditions, duloxetine 60 mg lowered pain intensity against placebo (SMD -0.31, 95% CI -0.39 to -0.24) [15].
- Population
- 5,318 participants with back pain, sciatica or osteoarthritis in 33 trials [17]; 4,959 participants in 18 studies for pain intensity [15].
- Sources
- [17], [15], [18]
- Caveats
- Certainty was moderate for back pain and low for osteoarthritis [17]. Duloxetine is the only SNRI with a chronic musculoskeletal pain approval [18]. Most trials were short and excluded people with low mood [15].
Endometriosis pain after surgery (hormonal IUD)
Small trials found period pain fell more at 12 months with a hormonal IUD placed after endometriosis surgery than with no further treatment, at low certainty.
Compared with expectant management after surgery [34]
The numbers and sources
- Effect
- In one trial, the median fall in period pain on a visual analogue scale was 81 with the levonorgestrel IUD against 50 with no further treatment (P = 0.006, 55 women). In another, pain fell 50 points against 30 (P = 0.021, 40 women). The trials could not be pooled. Satisfaction was higher with the IUD, 75% against 50% in one trial [34].
- Population
- 157 women having surgery for endometriosis in 4 RCTs [34].
- Sources
- [34]
- Caveats
- Certainty was low to very low, from risk of bias and imprecision. No trial reported overall pain [34].
Long COVID
Limited evidence: fatigue, brain fog, sleep and pain improved from baseline in uncontrolled studies of long COVID. No randomized trials were found.
The numbers and sources
- Effect
- A 2026 systematic review screened 397 records and found no randomized trials. In 4 pre-post studies (155 people) at 1 to 6 mg a day, fatigue (Hedges' g -0.74, 95% CI -1.11 to -0.37), brain fog (g -0.53), sleep (g -0.60), pain (g -0.93) and daily function (g -0.93) improved from baseline [12].
- Population
- 155 people with long COVID in the US and Ireland in uncontrolled studies [12].
- Sources
- [12]
- Caveats
- The review rated certainty as low, and its studies had no control group [12]. No peer-reviewed randomized trial was located.
Methocarbamol for acute low back pain
One trial found 44% on methocarbamol stopped treatment early with complete pain relief, against 18% on placebo, in acute low back pain with spasm.
The numbers and sources
- Effect
- Over up to 8 days, 44% on methocarbamol and 18% on placebo ended treatment early because pain was gone, and 19% against 52% stopped because treatment was judged not to be helping. At the final visit 67% on methocarbamol and 35% on placebo rated the treatment as having helped. Adverse events were reported by 5 patients [7].
- Population
- 202 adults with acute low back pain for at least 24 hours with spasm and restricted movement, 98 on methocarbamol and 104 on placebo [7].
- Sources
- [7]
- Caveats
- One trial, run in 2002 and analyzed after the fact for publication in 2015 [7]. A systematic review found very limited or inconsistent data for methocarbamol against placebo [4].
Endometriosis pain: norethindrone acetate compared with dienogest
One small trial found norethindrone acetate 5 mg and dienogest 2 mg eased endometriosis pain in women to a similar degree over 12 months, with fewer dropouts on norethindrone acetate.
Compared with dienogest [13]; dienogest, in consecutive patients before and after a clinic switched drugs [14]
The numbers and sources
- Effect
- Period pain scores fell from 7.43 and 7.23 to 0 in women completing 12 months on either drug, and pelvic pain scores did not differ significantly. Endometriomas shrank more on norethindrone acetate (p = 0.037). By 6 months, 47.5% on dienogest and 23.3% on norethindrone acetate had dropped out (p = 0.026) [13]. In a clinic that changed its first-choice drug, 71% on norethindrone acetate 2.5 mg and 72% on dienogest were satisfied or very satisfied at 6 months. Treatment was well tolerated by 58% and 80% [14].
- Population
- 70 women aged 18 to 40, 30 on norethindrone acetate and 40 on dienogest, in Turkey [13]. 90 consecutive women on each drug in Italy [14].
- Sources
- [13], [14]
- Caveats
- No placebo group. Scores at 12 months come from women who stayed on treatment [13]. The second study was not randomized [14].
Knee osteoarthritis pain
One trial found knee pain scores fell about 1.5 points more than placebo in people with knee osteoarthritis. The placebo group also improved.
The numbers and sources
- Effect
- In people with knee osteoarthritis, the WOMAC pain score changed by -3.4, -3.9 and -4.1 on 4, 9 and 12 mg, against -2.5 on placebo by intention to treat, differences of -1.4 and -1.6 points for 9 mg and 12 mg [1].
- Population
- 574 participants with knee osteoarthritis within TRIUMPH-1 [1].
- Sources
- [1]
- Caveats
- A subgroup of one trial. The placebo group also improved by 2.5 points.
Nerve pain after chemotherapy
One trial found duloxetine lowered pain from chemotherapy nerve damage by 0.73 points more than placebo on a 10-point scale over 5 weeks.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Average pain fell by 1.06 points on duloxetine and 0.34 on placebo, a difference of 0.73 (95% CI 0.26 to 1.20) on a scale of 0 to 10. Any decrease in pain was reported by 59% on duloxetine and 38% on placebo [22].
- Population
- 231 adults with painful neuropathy after taxane or oxaliplatin chemotherapy, in a crossover trial of 30 mg for one week then 60 mg for four weeks [22].
- Sources
- [22]
- Caveats
- One trial of 5 weeks per period. Not an approved use.
Gout flares
Mixed results: no fewer gout attacks than placebo over 30 days in one small trial, and flares became less frequent with continued treatment in longer trials.
The numbers and sources
- Effect
- Over 30 days, gout attacks occurred in 2 of 26 people on allopurinol 300 mg and 3 of 25 on placebo (RR 0.64, 95% CI 0.12 to 3.52) [1]. Over weeks 9 to 52 of a year-long trial, 64% on allopurinol had a flare, and the incidence fell with continued treatment [2]. In the final 24 weeks of a 72-week trial, 36.5% on allopurinol had one or more flares against 43.5% on febuxostat, meeting the test for noninferiority [4]. The label states that gout attacks usually become shorter and less severe after several months of treatment [5].
- Population
- 51 people in the placebo-controlled trial [1]; 760 people with gout [2]; 940 people with gout [4].
- Sources
- [1], [2], [4], [5]
- Caveats
- The longer trials had no placebo group, so the fall in flares over time has no untreated comparison [2][4].
Chronic prostatitis and pelvic pain
Mixed results: alpha-blockers lowered chronic prostatitis symptom scores about 5 points more than placebo, but a Cochrane review rated the evidence very low certainty.
Compared with placebo [15]
The numbers and sources
- Effect
- Total NIH Chronic Prostatitis Symptom Index scores fell 5.01 points more than on placebo in the short term (95% CI 2.61 to 7.41, 18 studies) and 5.60 points more in the long term (95% CI 0.32 to 10.89, 4 studies). The review set its clinically important difference at a six-point drop or 25% of baseline. Sexual function, quality of life, anxiety and depression differed little [15].
- Population
- 2,061 men with chronic prostatitis or chronic pelvic pain syndrome in 24 trials [15].
- Sources
- [15]
- Caveats
- Very low quality evidence, and the review authors were uncertain of the effect [15].
Nerve pain
Mixed results: Cochrane reviews found no unbiased evidence for amitriptyline or nortriptyline in nerve pain, while a broader meta-analysis found tricyclics needed fewer treated per responder than other classes.
Compared with placebo [3][4][5]; gabapentin, morphine and other antidepressants [5]
The numbers and sources
- Effect
- Across 17 amitriptyline studies, only third-tier evidence existed, and amitriptyline beat placebo in two of seven studies reporting usable efficacy data. At least one adverse event occurred in 55% on amitriptyline and 36% on placebo (RR 1.5, 95% CI 1.3 to 1.8) [3]. In a meta-analysis of 229 studies of nerve pain drugs, numbers needed to treat were lower for tricyclic antidepressants than the 6.4 to 7.7 found for SNRIs, pregabalin and gabapentin [4]. Nortriptyline trials gave very low quality evidence of efficacy similar to gabapentin, morphine, chlorimipramine, amitriptyline and placebo [5].
- Population
- 1,342 adults in 17 studies across seven nerve pain conditions [3]; 229 studies of oral and topical drugs [4]; 310 adults in six nortriptyline studies [5].
- Sources
- [3], [4], [5]
- Caveats
- Most amitriptyline studies were small and at high risk of bias. The Cochrane authors write that the concern is overestimation of the effect, not proof of no effect [3].
Fibroid pain and fibroid size: relugolix
Shown to ease fibroid pain and shrink the uterus against placebo. Relugolix combination therapy did not shrink the fibroids themselves, while relugolix alone did.
The numbers and sources
- Effect
- Relugolix combination therapy improved pain, distress from bleeding and pelvic discomfort, and uterine volume against placebo, but not fibroid volume [1]. Pooled across 6 studies, myoma volume fell 28.50% more than on placebo and uterine volume also fell more (reported as -30.31, p = 0.0028), with higher odds of pain relief (OR 9.02). Relugolix alone shrank myomas and the uterus more than combination therapy [3].
- Population
- 770 premenopausal women with fibroids [1]; 511 participants in 6 studies [3].
- Sources
- [1], [3]
- Caveats
- The pooled size results mix relugolix alone, which is not the US-approved form, with combination therapy [3].
Fibromyalgia pain
Mixed results: two meta-analyses found less fibromyalgia pain than placebo, while a third and two later trials found no difference.
The numbers and sources
- Effect
- In 4 RCTs (222 patients), pain scores fell more than on placebo (MD -0.86, 95% CI -1.20 to -0.51, I² 33%), while the revised Fibromyalgia Impact Questionnaire did not differ [1]. A meta-analysis of 5 RCTs found less pain than placebo (SMD -0.61, 95% CI -1.14 to -0.08) and no change in mechanical pain threshold [2]. A third meta-analysis of 8 trials found no difference from placebo in pain (SMD -0.50, 95% CI -1.19 to 0.19, I² 91%) or symptom severity [3]. In a crossover trial of 58 patients, 4.5 mg a day did not differ from placebo in pain ratings or questionnaire scores [4]. In 98 women followed for 12 months, pain at 3 months fell 0.33 points on LDN and 0.64 on placebo (difference 0.49, p 0.236) [5].
- Population
- Adults with fibromyalgia in small RCTs [1][2][3], 58 patients in a crossover trial with treatment periods of about 3 weeks [4], and 98 women over 12 months [5].
- Sources
- [1], [2], [3], [4], [5]
- Caveats
- The meta-analyses reach different answers from overlapping trials. Most trials were crossover designs with fewer than 60 people. The two trials published after the meta-analyses found no difference [4][5].
Endometriosis pain, compared with combined birth control pills
Mixed results: pooled trials found no clear difference in pelvic pain between progestin and combined birth control pills in women with endometriosis. Another review's results varied by pain type.
Compared with combined oral contraceptives [5][12]
The numbers and sources
- Effect
- Pelvic pain did not differ between oral progestins and combined pills (MD 0.38, 95% CI -0.46 to 1.22, moderate certainty), and side effects overall did not differ (RR 1.13, 95% CI 0.8 to 1.60). Pain-related quality of life was higher with progestins (SF-36 pain MD 11.5, 95% CI 2.35 to 20.65, low certainty) [5]. In another review of 8 trials, dienogest lowered overall pain scores more than a drospirenone pill (SMD -1.66, 95% CI -3.16 to -0.15), but eased pelvic pain (SMD 0.42) and pain during sex (SMD 0.70) less than combined pills. Side effects did not differ, except more hand numbness and weight gain on the pills [12].
- Population
- Women with endometriosis in 4 trials [5] and 8 trials [12].
- Sources
- [5], [12]
- Caveats
- Few small trials, and the certainty for most outcomes was low or very low [5].
Nerve pain after spinal cord injury
Limited evidence: two trials behind pregabalin's approval found lower pain scores than placebo, while a Cochrane review judged the evidence in central nerve pain inadequate.
The numbers and sources
- Effect
- The pregabalin label describes two placebo-controlled trials in spinal cord injury pain. In the 12-week trial, 150 to 600 mg a day improved the weekly mean pain score and raised the share of people with at least 30% and 50% pain reduction [7]. A Cochrane review of pregabalin concluded that evidence of efficacy in central neuropathic pain was inadequate [2].
- Population
- Adults with spinal cord injury pain lasting at least three months, with a baseline pain score of 6.5 to 6.7 out of 10 [7].
- Sources
- [7], [2]
- Caveats
- The label text read here gives no effect sizes. The evidence is for pregabalin.
Acute low back pain
Not shown to lower pain, disability or time to recovery in adults with acute low back pain at up to 4 g a day.
The numbers and sources
- Effect
- In a trial of 1,652 people, median time to recovery was 17 days on regular paracetamol, 17 days on as-needed paracetamol and 16 days on placebo (regular against placebo HR 0.99, 95% CI 0.87 to 1.14). Adverse events were reported by 18.5%, 18.7% and 18.5% [10]. Pooled, paracetamol did not lower pain intensity (mean difference -0.5 on a 0 to 100 scale, 95% CI -2.9 to 1.9) or disability (0.4, 95% CI -1.7 to 2.5) in the short term [9]. A Cochrane review found no difference from placebo at 1, 2, 4 and 12 weeks in pain, function, quality of life or sleep quality at 4 g a day [11].
- Population
- 1,652 adults with acute low back pain, 550 on regular dosing, 549 on as-needed dosing and 553 on placebo [10]; 13 randomized trials [9]; 1,825 participants in 3 trials [11].
- Sources
- [10], [9], [11]
- Caveats
- The Cochrane review included 3 trials and pooled 2. For chronic low back pain it found only very low-quality evidence, from one trial that was later retracted [11].
Sciatica and low back pain
Not shown to reduce leg pain from sciatica or chronic low back pain against placebo, in one large trial and two meta-analyses.
The numbers and sources
- Effect
- In a trial of pregabalin for sciatica, leg pain at week 8 scored 3.7 on pregabalin and 3.1 on placebo (adjusted difference 0.5, 95% CI -0.2 to 1.2), and at week 52 it was 3.4 against 3.0. No secondary outcome differed, and there were 227 adverse events on pregabalin against 124 on placebo [8]. A meta-analysis found high-quality evidence of no effect of gabapentinoids on chronic low back pain in the short term (mean difference -0.0, 95% CI -0.8 to 0.7) or on lumbar radicular pain (mean difference -0.1, 95% CI -0.7 to 0.5) [9]. A second meta-analysis found gabapentin gave minimal improvement in chronic low back pain against placebo, and that pregabalin did worse than other analgesics [10].
- Population
- 209 patients with sciatica followed for a year [8]; 859 participants in 9 trials [9]; 8 trials, with 185 participants in the gabapentin comparison [10].
- Sources
- [8], [9], [10]
- Caveats
- Not an approved use. Evidence quality was very low in [10], and high for the main comparisons in [9].
Pain after surgery
Not shown to reduce pain after surgery by a clinically meaningful amount: scores were 3 to 10 points lower on a 100-point scale across 281 trials.
The numbers and sources
- Effect
- Gabapentinoids given around surgery lowered pain intensity on a 100-point scale by 10 points at 6 hours, 9 at 12 hours, 7 at 24 hours and 3 at 48 hours, each below the 10-point threshold for a meaningful difference. There was no effect at 72 hours or on later chronic pain. Nausea and vomiting were less frequent, and dizziness and visual disturbance more frequent [18].
- Population
- 24,682 participants in 281 trials [18].
- Sources
- [18]
- Caveats
- Not an approved use. Results were the same for gabapentin and pregabalin.
Nerve pain and fibromyalgia
Not shown to relieve nerve pain in adults at 200 to 400 mg a day, in a Cochrane review of 12 trials. Almost 10% on lamotrigine reported a rash.
Compared with placebo [9]
The numbers and sources
- Effect
- No study gave first-tier evidence for an efficacy outcome, and the review found no convincing evidence of pain relief at doses of 200 to 400 mg daily. Almost 10% of participants taking lamotrigine reported a skin rash [9].
- Population
- 1,511 adults with diabetic nerve pain, HIV-related nerve pain, post-stroke pain, spinal cord injury pain, chemotherapy nerve pain, trigeminal neuralgia or mixed nerve pain, in 12 studies mostly 8 weeks or longer [9].
- Sources
- [9]
- Caveats
- No fibromyalgia trial was found, so the fibromyalgia part of the question rests on no data [9].
Chronic pain across conditions
Not shown to improve pain or quality of life across chronic pain conditions, with less pain than placebo only in fibromyalgia in one analysis.
The numbers and sources
- Effect
- In a meta-analysis of 7 RCTs, pain response did not differ from control overall (d -0.11, 95% CI -0.96 to 0.74). Against placebo in fibromyalgia, pain was lower (d -0.34, 95% CI -0.62 to -0.06). Against active drugs, there was no difference [6]. A systematic review of 7 RCTs (406 patients) at 2 to 4.5 mg a day found no improvement in pain or quality of life across chronic pain conditions [7]. In 23 people with osteoarthritis or inflammatory arthritis, 8 weeks of 4.5 mg did not change pain interference (-23 points against -22 on placebo, p 0.90), pain severity or fatigue [8].
- Population
- Adults with chronic pain conditions, including fibromyalgia [6][7], and 17 people with osteoarthritis and 6 with inflammatory arthritis [8].
- Sources
- [6], [7], [8]
- Caveats
- The arthritis trial was a pilot too small to rule out a modest effect [8].
Added to an NSAID for acute low back pain
Not shown to improve function or pain at 1 week when added to naproxen or ibuprofen for acute low back pain in two emergency department trials.
The numbers and sources
- Effect
- In people sent home from an emergency department with naproxen, function at 1 week improved 10.1 points on a 24-point scale with cyclobenzaprine added and 9.8 points with placebo added (difference 0.3, 98.3% CI -2.6 to 3.2) [5]. In people sent home with ibuprofen, function improved 11.1 points with placebo added, 10.6 with baclofen, 10.1 with metaxalone and 11.2 with tizanidine. Moderate to severe pain at 1 week was reported by 30% on placebo, 33% on baclofen and 33% on tizanidine [6].
- Population
- 323 adults with acute low back pain of 2 weeks or less, 108 assigned cyclobenzaprine 5 mg [5]; 320 adults with acute low back pain of 2 weeks or less in 4 groups [6].
- Sources
- [5], [6]
- Caveats
- Both trials came from emergency departments in one city and followed people for 1 week as the main outcome.
Acute low back, neck and limb pain
Not shown to relieve acute low back, neck or limb pain more than placebo or non-opioid pain relievers in three randomized trials.
The numbers and sources
- Effect
- In adults with acute low back or neck pain, pain at 6 weeks was 2.78 on a 10-point scale on oxycodone with naloxone and 2.25 on placebo (adjusted difference 0.53, 95% CI -0.00 to 1.07). Constipation was reported by 7.5% and 3.5% [3]. In emergency department patients with acute low back pain who were all given naproxen, adding oxycodone with acetaminophen did not improve function at 1 week more than adding placebo (difference 1.3 points on a 24-point scale, 98.3% CI -1.5 to 4.1) [4]. In emergency department patients with acute arm or leg pain, pain fell at 2 hours by 4.3 points of 10 on ibuprofen plus acetaminophen, 4.4 on oxycodone plus acetaminophen, 3.5 on hydrocodone plus acetaminophen and 3.9 on codeine plus acetaminophen, with no significant difference [5].
- Population
- 347 adults with 12 weeks or less of low back or neck pain, treated for up to 6 weeks [3]; 323 adults with acute low back pain, 108 of them assigned oxycodone with acetaminophen [4]; 416 adults aged 21 to 64 with moderate to severe acute extremity pain [5].
- Sources
- [3], [4], [5]
- Caveats
- The limb pain trial gave one dose and did not assess adverse events [5]. The back and neck pain trial used oxycodone combined with naloxone [3].
Cancer pain, compared with morphine
Not shown to differ from morphine in the share of people with cancer pain relieved, with less constipation on controlled-release oxycodone.
The numbers and sources
- Effect
- Across 13 studies, the share with complete or significant pain relief did not differ between controlled-release oxycodone and controlled-release morphine (RR 1.02, 95% CI 0.95 to 1.10). Pain intensity was slightly lower on morphine (SMD 0.14, 95% CI 0.01 to 0.27), equal to 0.27 points on a 0 to 10 scale. Constipation was less frequent on oxycodone (RR 0.75, 95% CI 0.66 to 0.86). Controlled-release and immediate-release oxycodone did not differ in pain intensity [13].
- Population
- 4,485 participants with cancer pain in 42 studies [13].
- Sources
- [13]
- Caveats
- No placebo-controlled comparison. The reviewers rated the certainty low or very low [13].
Gout flares, compared with NSAIDs
Not shown to differ from indomethacin or naproxen in pain relief for a gout flare in two randomized trials.
The numbers and sources
- Effect
- In emergency departments, pain fell by about 25 mm at rest and 45 mm with activity on a 100 mm scale over 14 days on both prednisolone and indomethacin. Minor adverse events in the emergency department were less frequent on prednisolone (6% against 19%) and equal over 14 days (37% each) [7]. In primary care, pain at 90 hours had fallen 44.7 mm on prednisolone and 46.0 mm on naproxen (difference 1.3 mm, 95% CI -9.8 to 7.1), with similar adverse effects [8].
- Population
- 416 adults with acute gout in 4 Hong Kong emergency departments, 376 completing [7]; 120 primary care patients with crystal-confirmed gout, given prednisolone 35 mg or naproxen 500 mg twice a day for 5 days [8].
- Sources
- [7], [8]
- Caveats
- Neither trial had a placebo group. In the larger trial gout was usually diagnosed on clinical criteria [7].
Chronic low back pain
One trial found low-dose amitriptyline did not reduce back pain more than an active placebo at 6 months, with less disability at 3 months only.
Compared with an active placebo, benztropine [11]
The numbers and sources
- Effect
- Pain did not differ at 6 months (adjusted difference -7.81, 95% CI -15.7 to 0.10) or 3 months. Disability was lower at 3 months (adjusted difference -1.62, 95% CI -2.88 to -0.36) but not at 6 months. Withdrawals for adverse events were 12% in each group [11].
- Population
- 146 adults with chronic nonspecific low back pain, 118 completing 6 months [11].
- Sources
- [11]
- Caveats
- One modest-sized trial at 25 mg a day [11].
Acute low back pain
One trial found diazepam added to naproxen did not improve acute low back pain or function more than placebo at one week or three months.
The numbers and sources
- Effect
- Disability scores improved by 11 points in both the diazepam and placebo groups at one week. Moderate or severe pain at one week was reported by 32% on diazepam and 22% on placebo, and at three months by 12% and 9%. Adverse events were reported by 21% on diazepam and 15% on placebo [17].
- Population
- 114 emergency department patients with acute low back pain, all given naproxen [17].
- Sources
- [17], [8]
- Caveats
- One trial of 114 people. The diazepam label lists muscle spasm as an add-on use [8].
Endometriosis pain
One small trial found naproxen did not clearly relieve endometriosis pain more than placebo, in very low-quality evidence.
Compared with placebo [26]
The numbers and sources
- Effect
- Pain relief on naproxen did not differ clearly from placebo (OR 3.27, 95% CI 0.61 to 17.69, 24 women). The need for extra pain medicine (OR 0.12, 95% CI 0.01 to 1.29) and side effects (OR 0.46, 95% CI 0.09 to 2.47) were inconclusive [26].
- Population
- 24 women with endometriosis in one crossover trial, the only one of two included trials that could be analyzed [26].
- Sources
- [26]
- Caveats
- One small trial with unclear risk of bias. The review found no new trials in its 2016 update, and no data on quality of life or daily activities [26].
Peptides and SARMs
Knee pain
One small uncontrolled study found 14 of 16 patients reported knee pain relief after BPC-157 injections, some combined with thymosin beta-4.
Compared with the same patients' recall of their pain before the injection, with no other group [14]
The numbers and sources
- Effect
- A chart review at one US clinic reached 16 patients by phone 6 months to 1 year after a knee injection. Of 12 who received BPC-157 alone, 11 reported significant improvement in knee pain. Of 4 who received BPC-157 with thymosin beta-4, 3 reported significant improvement. Overall, 14 of 16 (87.5%) reported relief. No tools were used to measure function, stiffness, quality of life or daily activities [14]. A 2026 systematic review judged the study of poor methodological quality and rated the certainty of evidence very low [9].
- Population
- 16 patients with knee pain of several causes, from a chart review covering 2019 to 2020 [14].
- Sources
- [14], [9], [10]
- Caveats
- Retrospective, uncontrolled and unblinded, with pain recalled in a phone survey [14]. With no comparison group, the study cannot separate an effect of the injection from placebo response or natural recovery. A 2026 review describes human musculoskeletal evidence for BPC-157 as limited to this one small case series without validated outcome measures [10].
Supplements
Knee osteoarthritis pain and function
Shown to lower knee osteoarthritis pain and stiffness and improve function against control in adults, in mostly small, low-quality trials.
The numbers and sources
- Effect
- In 7 trials (545 patients), boswellia lowered VAS pain (WMD -8.33, 95% CI -11.19 to -5.46) and WOMAC pain (WMD -14.22), stiffness (WMD -10.04) and function scores (WMD -10.75) against control [1]. A meta-analysis of 11 RCTs (1,009 patients) of curcuminoids and boswellia found both improved pain and function more than placebo [2]. A 2026 network meta-analysis of 20 RCTs (1,633 participants) found modified boswellia formulations improved WOMAC pain, stiffness and function [3].
- Population
- Adults with knee osteoarthritis, mostly mild to moderate [1][2][3].
- Sources
- [1], [2], [3]
- Caveats
- Study quality was low overall, and most trials had fewer than 100 participants. No RCT compared boswellia with approved NSAIDs [2]. The abstracts do not report trial funding.
Pain after wisdom tooth surgery
Shown to lower pain after wisdom tooth surgery in adults, though reviews of the same small trials disagree on when the effect appears.
The numbers and sources
- Effect
- In 6 RCTs against placebo, bromelain lowered pain 7 days after surgery (SMD -0.54, 95% CI -0.87 to -0.20) but not in the first 2 to 3 days [1]. A second meta-analysis of 4 studies found lower pain (MD -0.38, 95% CI -0.66 to -0.09) [2]. A third, of 5 trials (252 patients), found lower pain at 48 to 72 hours (MD -0.89, 95% CI -1.70 to -0.09) [3]. A fourth, of 6 RCTs, found lower pain in the first 24 hours (SMD -0.49, 95% CI -0.82 to -0.17) and at 7 days (SMD -0.52), with better ratings of appearance, social isolation and sleep in the first week [4].
- Population
- Adults having lower third molar surgery [1][2][3][4].
- Sources
- [1], [2], [3], [4]
- Caveats
- The four reviews drew largely on the same small trials. Timing of the pain effect differs between them.
Period pain
Shown in two reviews to lower period pain more than controls in women with dysmenorrhea, at 300 to 1,800 mg a day for 2 to 3 months.
Compared with control groups the source abstracts do not describe [54][55]
The numbers and sources
- Effect
- Across 12 studies (881 women) giving 300 to 1,800 mg of long-chain omega-3 a day for 2 or 3 months, 8 pooled studies showed lower pain (Cohen's d -1.020, 95% CI -1.53 to -0.51). 86% of studies that measured pain medicine use found it fell, and few mild side effects were reported [54]. A second review of RCTs found lower primary dysmenorrhea severity (SMD -1.075, 95% CI -1.871 to -0.279), with smaller effects at higher daily intakes and in older women [55].
- Population
- 881 women with dysmenorrhea in 12 studies [54]; women with primary dysmenorrhea in RCTs [55].
- Sources
- [54], [55]
- Caveats
- Most studies were rated neutral in quality [54]. The trials were small and short, and the two reviews share many of them.
Period pain
Shown in three reviews to lower period pain more than placebo in women with primary dysmenorrhea, by about 1.1 to 1.6 points on a 10-point scale.
Compared with placebo or standard care [63]; placebo, in trials that had a placebo group [64]; placebo [65]
The numbers and sources
- Effect
- Across 8 RCTs (695 participants), vitamin D lowered pain more than placebo (SMD -1.404, 95% CI -2.078 to -0.731), with relief at average weekly doses over 50,000 IU [63]. Across 11 studies (687 participants), pain intensity fell 1.64 points more than in controls (95% CI 1.00 to 2.27, I² 79%), with moderate certainty. Pain fell in primary dysmenorrhea (MD -1.90) but not in the 3 trials of secondary dysmenorrhea [64]. A review of registered trials found pain 1.12 points lower than placebo on a visual analogue scale (95% CI 0.07 to 2.16, 5 studies, 308 participants), in the primary dysmenorrhea trials only [65].
- Population
- Women with primary dysmenorrhea in 8 RCTs [63]; women with regular periods and primary or secondary dysmenorrhea in 11 RCTs, 7 of them in Iran [64]; 7 registered RCTs in primary dysmenorrhea or endometriosis [65].
- Sources
- [63], [64], [65]
- Caveats
- Heterogeneity was high [64][65]. Doses and schedules varied widely, and the registered trials had high or some concerns of risk of bias [65]. The three reviews share many trials.
Diabetic nerve damage, IV treatment
Shown to raise nerve conduction speed in people with diabetic neuropathy when given by IV for 2 to 4 weeks. Most trials were poor quality.
The numbers and sources
- Effect
- IV alpha-lipoic acid at 300 to 600 mg a day for 2 to 4 weeks raised nerve conduction velocity by 3.2 to 4.6 m/s across four nerves, and overall improvement was 4 times as likely as on control (OR 4.03, 95% CI 2.73 to 5.94) [1].
- Population
- 15 randomized trials in diabetic peripheral neuropathy [1].
- Sources
- [1]
- Caveats
- The authors note most trials were of poor quality [1].
Diabetic nerve symptoms, oral treatment
Shown to lower nerve symptom scores in people with diabetic neuropathy over 5 weeks. Over 4 years, the main combined measure did not change.
The numbers and sources
- Effect
- Over 5 weeks, total symptom scores fell 51% on 600 mg a day, 48% on 1,200 mg and 52% on 1,800 mg, against 32% on placebo (all P < 0.05) [2]. Over 4 years, 600 mg a day did not change the primary composite of impairment and nerve tests (P = 0.105). Impairment scores improved on secondary measures (NIS, P = 0.028) [3]. A 2026 network meta-analysis ranked oral alpha-lipoic acid first for lower-limb impairment scores (NIS-LL, SUCRA 97.4%, I² 0%). IV ranked first for symptom scores, and both routes raised global satisfaction [4]. A 2026 meta-analysis found lower paresthesia (SMD -1.04, 95% CI -1.24 to -0.84) and numbness (SMD -0.23, 95% CI -0.44 to -0.01) scores, mostly at 600 mg a day. HbA1c and two nerve conduction measures did not change [5].
- Population
- 181 people with diabetic polyneuropathy in Russia and Israel [2]; 460 people with mild to moderate diabetic polyneuropathy [3]; 9 randomized trials of 600 to 1,800 mg a day for 3 to 208 weeks [4]; 15 studies in diabetic neuropathy [5].
- Sources
- [2], [3], [4], [5]
- Caveats
- In the 4-year trial, the placebo group did not worsen, so the trial could not test prevention of decline as designed [3]. The abstract of [5] does not separate oral from IV use, and some comparisons were against other treatments.
Osteoarthritis pain
Shown to reduce osteoarthritis pain and disability modestly in adults over placebo.
The numbers and sources
- Effect
- In 5 placebo-controlled trials (593 patients), ginger reduced pain (SMD -0.30, 95% CI -0.50 to -0.09, I² 27%) and disability (SMD -0.22, 95% CI -0.39 to -0.04) [6].
- Population
- Adults with osteoarthritis [6].
- Sources
- [6]
- Caveats
- The authors rated the evidence moderate quality because trials were small and lacked proper intention-to-treat analysis [6].
Period pain
Shown to lower period pain scores in women with primary dysmenorrhea when taken in the first 3 to 4 days of the cycle.
The numbers and sources
- Effect
- In 4 placebo-controlled RCTs, ginger during the first 3 to 4 days of the cycle lowered pain scores (reported as -1.85, 95% CI -2.87 to -0.84) [7].
- Population
- Women with primary dysmenorrhea in 7 RCTs, 4 pooled [7].
- Sources
- [7]
- Caveats
- Four pooled trials. The search included Korean, Chinese and Indian databases [7].
Chondroitin and pain in shorter trials
Shown to lower pain about 10% in trials under 6 months in people with osteoarthritis, mostly of the knee. Reviews disagree on whether this is meaningful.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Across 43 RCTs, chondroitin lowered pain by an absolute 10% (95% CI 6 to 15%) in studies under 6 months, with I² 70% and low-quality evidence. A 20% reduction in knee pain was reached by 53 per 100 on chondroitin and 47 per 100 on placebo (RR 1.12, 95% CI 1.01 to 1.24, 2 trials, high-quality evidence) [4].
- Population
- 4,962 participants on chondroitin and 4,148 controls, mostly knee osteoarthritis, 1 month to 3 years [4].
- Sources
- [4]
- Caveats
- This review and the network meta-analysis disagree on whether chondroitin's pain effect is clinically meaningful [1][4]. High heterogeneity was not explained by bias or sample size [4].
Knee osteoarthritis pain and function
Shown to improve knee osteoarthritis physical function scores over placebo in adults, with pain results mixed and gains called small.
The numbers and sources
- Effect
- On 6 g a day for 12 weeks, WOMAC pain and physical function improved against placebo (P < 0.05). Stiffness and total symptom scores did not change [1]. On 3.4 g a day for 12 weeks, WOMAC physical function (14.6 mm, P = 0.04) and total score (15.0 mm, P = 0.03) improved. WOMAC pain did not reach significance (P = 0.08) [2]. On 1.5 g a day, the pain index fell from 1.53 to 0.74, and more with glucosamine added [3]. A 2008 review called the MSM trials positive but not definitive [4].
- Population
- 50 adults aged 40 to 76 [1]; 49 adults aged 45 to 90 [2]; 118 people with mild to moderate knee osteoarthritis [3]; 168 people in 2 MSM trials [4].
- Sources
- [1], [2], [3], [4]
- Caveats
- The authors of [2] call the improvements small and of uncertain clinical significance. The review raised concerns about dose and treatment length [4].
Period pain
Shown to lower period pain against placebo or NSAIDs in women with primary dysmenorrhea, in few trials with high heterogeneity.
The numbers and sources
- Effect
- Across 5 controlled trials (201 women on valerian, 207 controls), valerian reduced primary dysmenorrhea pain against placebo or NSAIDs (SMD -1.03, 95% CI -1.74 to -0.33, I² 90.40%) [5].
- Population
- Women with primary dysmenorrhea in RCTs published from 2000 to 2023 [5].
- Sources
- [5]
- Caveats
- Heterogeneity was high, the trials were few, and the comparators mixed placebo and NSAIDs. Doses and trial designs varied [5].
Endometriosis pain, with vitamin C
Shown in pooled trials to ease pelvic pain, period pain and pain with sex in women with endometriosis when vitamin E was taken with vitamin C.
Compared with placebo [19][20][21]
The numbers and sources
- Effect
- Across 5 RCTs of vitamins C and E together, more women reported less chronic pelvic pain (RR 7.30, 95% CI 3.27 to 16.31), less period pain (RR 1.96, 95% CI 1.25 to 3.07) and less pain with sex (RR 5.08, 95% CI 2.10 to 12.26) than on placebo [19]. A review of 13 RCTs found vitamin E, with or without vitamin C, improved pelvic pain [20]. In one trial, 1,200 IU of vitamin E with 1,000 mg of vitamin C for 8 weeks improved everyday pain in 43% of women (P = 0.0055), with no change on placebo, and period pain fell in 37% [21].
- Population
- 5 RCTs in women with endometriosis [19]; 13 RCTs with 589 women [20]; 59 women aged 19 to 41 with pelvic pain and endometriosis or infertility [21].
- Sources
- [19], [20], [21]
- Caveats
- Vitamin E was given with vitamin C, so its share of the effect is not separated. Trials were small and lasted about 8 weeks. The second review's abstract gives no pooled size for vitamin E [20].
Cyclic breast pain
Shown to ease cyclic breast pain against placebo, with a moderate effect, and to lower raised prolactin in women of reproductive age.
Compared with placebo [5]; dopamine agonists, NSAIDs, serotonin reuptake inhibitors and hormonal contraceptives [5]
The numbers and sources
- Effect
- In 6 placebo-controlled studies, vitex reduced breast pain intensity (SMD 0.67, 95% CI 0.5 to 0.85). It lowered raised serum prolactin, and 7 trials found it not inferior to dopamine agonists, NSAIDs, serotonin reuptake inhibitors or hormonal contraceptives [5].
- Population
- 718 women aged 18 to 45 in the pooled studies, among 25 studies in the review [5].
- Sources
- [5]
- Caveats
- Risk of bias was unclear in most studies [5].
Period pain
Shown in one meta-analysis of 6 trials to lower period pain more than placebo, with larger effects at 8 weeks or longer.
Compared with placebo [18]; placebo or no treatment [19]
The numbers and sources
- Effect
- Across 6 RCTs, zinc lowered pain severity more than placebo (Hedges's g -1.541, 95% CI -2.268 to -0.814). Longer treatment (8 weeks or more) gave larger reductions (p = 0.003), and higher doses added a small amount per milligram. Adverse events did not differ significantly from placebo (OR 2.54, 95% CI 0.78 to 8.26) [18]. In a Cochrane review, zinc sulfate lowered pain by 0.95 points on a 0 to 10 scale against placebo in one trial (95% CI 0.36 to 1.54, 99 women) [19].
- Population
- 6 RCTs with 739 women with primary dysmenorrhea [18]; one RCT of 99 women within a review of 27 RCTs [19].
- Sources
- [18], [19]
- Caveats
- The Cochrane review rated its evidence low or very low quality [19]. The effect size in [18] is a standardized difference, not points on a pain scale.
Joint pain and arthritis
Small trials found boron supplements eased knee discomfort over 2 weeks and lowered inflammation markers in arthritis. Several were short, and one was run by the maker.
The numbers and sources
- Effect
- In 60 adults with self-reported knee discomfort, calcium fructoborate 110 mg twice a day lowered McGill Pain Questionnaire scores by 8.9 points and WOMAC scores by 13.73 points more than placebo at day 14 (both p < 0.0001), with no change on placebo [10]. In 60 adults with knee osteoarthritis, 15 days of calcium fructoborate improved C-reactive protein, fibrinogen and sedimentation rate against placebo, with no serious adverse events [11]. In 72 people with rheumatoid arthritis on etanercept, calcium fructoborate or borax (6 mg of boron a day) for 60 days improved disease activity scores and lowered ESR, hsCRP, IL-1α, IL-6 and TNF-α against placebo [12]. A 1994 review reported a 20-person trial in osteoarthritis in which 50% improved on 6 mg of boron a day against 10% on placebo [13].
- Population
- 60 adults aged 35 to 65 with knee discomfort in Mexico [10]. 60 middle-aged adults with knee osteoarthritis [11]. 72 adults with rheumatoid arthritis in Iraq [12]. 20 adults with osteoarthritis [13].
- Sources
- [10], [11], [12], [13]
- Caveats
- Trials ran 2 weeks to 2 months. The knee discomfort trial was designed by FutureCeuticals, which supplied the calcium fructoborate and employed most authors [10]. The 20-person trial is known only from its author's review [13]. No meta-analysis was located.
Period pain
One small trial found calcium alone lowered period pain 1.6 points on a 10-point scale more than placebo. Calcium with vitamin D did not differ significantly.
Compared with placebo [24]
The numbers and sources
- Effect
- Taken from day 15 of the cycle until pain ended in the next cycle, for 3 cycles, 1,000 mg of calcium lowered mean pain intensity by 1.6 points more than placebo (95% CI 0.6 to 2.6). Calcium with 5,000 IU of vitamin D3 lowered it by 0.7 points, which was not significant (95% CI -0.3 to 1.6). Menstrual blood loss did not differ from placebo in either group [24].
- Population
- 85 university students with moderate or severe primary dysmenorrhea in Iran [24].
- Sources
- [24]
- Caveats
- One small trial. Time and the interaction of time with group had no significant effect on pain [24].
Period pain
Small trials found magnesium relieved period pain more than placebo and cut the need for extra pain medicine, in a 2001 review.
Compared with placebo [18]
The numbers and sources
- Effect
- In three small trials, magnesium gave more pain relief than placebo, and less additional pain medication was needed. The number of adverse effects did not differ [18].
- Population
- Women with primary dysmenorrhea in three small randomized trials [18].
- Sources
- [18]
- Caveats
- The review is from 2001 and its abstract gives no pooled size of the effect. Doses and schedules varied between trials, and the authors could not name a dose or schedule from them [18].
Menstrual cycle complaints in routine care
One uncontrolled study by the manufacturer found most women reported lighter, less frequent bleeding and less period pain after 3 months, with no comparison group.
Compared with before treatment, in the same women [7]
The numbers and sources
- Effect
- After 3 months of a 4 mg extract, 83.4% reported improved bleeding intensity, 79.2% improved bleeding frequency and 85.2% less period pain. Irregular cycles fell from 9.1% to 0.1% of women and breast tenderness from 39.9% to 0.8%. Cycle and period length did not change meaningfully [7].
- Population
- 1,700 women with menstrual cycle complaints, mean age 30, mostly period pain (43.8%) and breast pain (21.1%), at one center [7].
- Sources
- [7]
- Caveats
- Retrospective, single center, no control group, outcomes collected partly by telephone. Five authors were employees of the manufacturer, which funded the data management, statistics and writing support [7].
Statin-associated muscle pain
Mixed results: two reviews found no benefit for statin muscle pain, including one limited to diagnosed statin myalgia, while two others found less pain.
The numbers and sources
- Effect
- Statin therapy lowered plasma CoQ10 by 0.44 μmol/L across 8 placebo-controlled arms [1]. For muscle pain, a 2015 meta-analysis of 6 RCTs found no significant effect (SMD -0.53, 95% CI -1.33 to 0.28) and no change in creatine kinase [2]. A 2020 meta-analysis of 7 RCTs (321 patients) found no benefit for myalgia (WMD -0.42, 95% CI -1.47 to 0.62) and no change in staying on statins (RR 0.99) [3]. A 2018 meta-analysis of 12 RCTs (575 patients) found less muscle pain (WMD -1.60, 95% CI -1.75 to -1.44), weakness and cramps [4]. A 2025 meta-analysis of 7 RCTs (389 patients) found less pain intensity (WMD -0.96, 95% CI -1.88 to -0.03) [5].
- Population
- Adults taking statins, many with muscle symptoms [2][3][4]. The 2025 review covered 100 to 600 mg a day for 30 to 90 days [5].
- Sources
- [1], [2], [3], [4], [5]
- Caveats
- The four reviews pool overlapping small trials with different inclusion rules and reach opposite conclusions. The review restricted to patients with diagnosed statin myalgia found no benefit [3]. Creatine kinase did not change in any of them [2][4].
Chronic pain and knee osteoarthritis
Mixed results: omega-3 lowered chronic pain but not osteoarthritis pain in one review, while krill oil reviews found better knee osteoarthritis pain scores.
The numbers and sources
- Effect
- Across 41 RCTs (3,759 participants), omega-3 lowered chronic pain intensity (SMD -0.55, 95% CI -0.76 to -0.34, I² 87%), from -0.27 at 1 month to -0.83 at 6 months. Effects were significant in rheumatoid arthritis, migraine and mixed chronic pain, and not in osteoarthritis or breast pain [27]. In knee osteoarthritis, krill oil improved WOMAC pain (SMD -0.60, 95% CI -0.99 to -0.21), stiffness and function across 5 RCTs (730 participants), with no change on a visual analog pain scale [28]. A 2026 review of 6 RCTs (971 participants) also found better WOMAC pain and function at week 4 [29].
- Population
- Adults with chronic pain conditions [27]; adults with knee osteoarthritis [28][29].
- Sources
- [27], [28], [29]
- Caveats
- Heterogeneity was high in [27]. The reviews disagree on osteoarthritis, though the krill reviews tested one product type. Lower doses (1.35 g a day or less) did as well as higher doses [27].
Glucosamine product type
Mixed results: trials of the Rotta preparation showed larger pain relief, while other preparations and well-concealed trials found no benefit.
The numbers and sources
- Effect
- Across 20 RCTs, glucosamine improved pain (SMD -0.61, 95% CI -0.95 to -0.28), but analyses limited to 8 trials with adequate allocation concealment found no benefit. Trials of the Rotta preparation showed pain SMD -1.31, while non-Rotta preparations showed SMD -0.15 (95% CI -0.35 to 0.05) [5].
- Population
- 2,570 patients in 20 RCTs [5].
- Sources
- [5]
- Caveats
- WOMAC pain, function and stiffness did not differ from placebo in this review. The 2005 search predates the large independent trials [2][3].
Endometriosis pain
Mixed results: three reviews found no significant drop in endometriosis pain on vitamin D, while one found less period pain in its vitamin D trials.
Compared with placebo [64][65][66][67]
The numbers and sources
- Effect
- Pain did not fall significantly in the 3 trials of secondary dysmenorrhea [64] or in the registered endometriosis trials [65]. A review of 13 RCTs found vitamin D lowered pelvic pain in endometriosis, a difference that was not significant against placebo [66]. A review of antioxidant supplements found less endometriosis-related period pain in the vitamin D trials (SMD -0.59, 95% CI -1.13 to -0.06, I² 70%) [67].
- Population
- 3 RCTs in secondary dysmenorrhea [64]; registered RCTs in endometriosis [65]; 13 RCTs with 589 women with endometriosis [66]; 10 RCTs of antioxidant supplements in endometriosis [67].
- Sources
- [64], [65], [66], [67]
- Caveats
- Trials were few and small, and heterogeneity was high [67].
Period pain
Mixed results: two reviews found vitamin E lowered period pain more than placebo, while a Cochrane review of two trials found no difference.
Compared with placebo [16][17]; placebo or no treatment [18]
The numbers and sources
- Effect
- Across 8 RCTs, vitamin E lowered primary dysmenorrhea pain more than placebo in the first month (SMD -1.16, 95% CI -2.16 to -0.17) and the second month (SMD -1.83, 95% CI -2.90 to -0.77), with no serious side effects reported [16]. A review of micronutrients found lower pain on vitamin E than placebo (SMD -0.47, 95% CI -0.74 to -0.20) [17]. A Cochrane review found no difference on a 0 to 10 pain scale (MD 0.00 points, 95% CI -0.34 to 0.34, 2 RCTs, 135 women) [18].
- Population
- 8 RCTs with 1,002 women with primary dysmenorrhea [16]; 16 trials with 1,871 participants aged 13 to 40, 4 of them of vitamin E [17]; 27 RCTs with 3,101 women, mostly students in their late teens or early twenties [18].
- Sources
- [16], [17], [18]
- Caveats
- Heterogeneity was high in the second month (I² 76%) [16]. The Cochrane review rated all its evidence low or very low quality, and most trials were from Iran [18]. The reviews included different trials.
Joint pain and osteoarthritis
Limited evidence: one trial found no change in knee osteoarthritis scores against placebo, and pooled studies across conditions found slightly lower pain.
The numbers and sources
- Effect
- In 47 adults with moderate to severe knee osteoarthritis, 800 mg a day for 12 weeks did not change the total WOMAC score against placebo (coefficient 11.16, 95% CI -8.86 to 31.18, p 0.27) [6]. In 40 adults with mild to moderate knee osteoarthritis, 500 mg a day did not differ from diclofenac 100 mg a day at 4 weeks [7]. Across 9 studies of oral bromelain in various conditions, pain scores were slightly lower than in controls (MD -0.27, 95% CI -0.45 to -0.08, I² 29%) [8]. An earlier review found that all trials before 2004 were uncontrolled or comparative [9].
- Population
- Adults with knee osteoarthritis [6][7]. Mixed conditions [8].
- Sources
- [6], [7], [8], [9]
- Caveats
- Only 31 of 47 finished the placebo trial [6]. The diclofenac trial was single-blind with no placebo [7]. The pooled pain estimate mixes conditions [8].
Knee and hip osteoarthritis pain
Not shown to lower osteoarthritis pain by a clinically important amount: about 0.3 to 0.5 cm on a 10 cm scale, and independent trials found no difference.
The numbers and sources
- Effect
- Across 10 trials (3,803 patients), pain on a 10 cm scale differed from placebo by -0.4 cm for glucosamine (95% credible interval -0.7 to -0.1), -0.3 cm for chondroitin and -0.5 cm for the combination. None reached the prespecified minimal clinically important difference of -0.9 cm [1]. In 1,583 patients over 24 weeks, response rates did not differ significantly from placebo (60.1%): 3.9 points higher with glucosamine, 5.3 with chondroitin and 6.5 with both. Celecoxib was 10.0 points higher [2]. Individual patient data from 5 industry-independent trials (1,625 people) found glucosamine no different from placebo at 3 and 24 months, in every predefined subgroup [3].
- Population
- Adults with knee or hip osteoarthritis [1][2][3].
- Sources
- [1], [2], [3]
- Caveats
- Industry-independent trials showed smaller effects than commercially funded trials (P = 0.02 for interaction) [1]. In GAIT, an exploratory subgroup with moderate to severe pain responded more to the combination (79.2% versus 54.3%) [2].
Pain
Not shown to relieve pain more than placebo in 15 of 16 trials of pharmaceutical-grade CBD across 12 pain conditions.
The numbers and sources
- Effect
- A 2024 review found 16 randomized trials of pharmaceutical-grade CBD with pain as an outcome, across 12 pain conditions, at 6 to 1,600 mg and from a single dose to 12 weeks. Fifteen of the 16 showed no benefit of CBD over placebo [7].
- Population
- Adults with a range of pain conditions [7].
- Sources
- [7]
- Caveats
- The review is not a pooled meta-analysis [7].
Osteoarthritis pain and function
Not shown to lower pain or improve function more than placebo in adults with knee or hip osteoarthritis.
The numbers and sources
- Effect
- In 4 trials (656 patients), pain was slightly lower than placebo, but not significantly (SMD -0.17, 95% CI -0.34 to 0.01), equal to 0.4 cm on a 10 cm scale. Function did not differ (SMD 0.02, 95% CI -0.68 to 0.71) [6].
- Population
- Adults with knee or hip osteoarthritis [6].
- Sources
- [6]
- Caveats
- The review rated trial quality and reporting as poor and called itself inconclusive [6].
Knee osteoarthritis pain
One trial found knee pain scores did not differ significantly from placebo in adults with knee osteoarthritis, though CRP fell.
The numbers and sources
- Effect
- In 58 patients drinking two 8 oz bottles a day for 6 weeks, WOMAC scores fell during cherry juice but the difference from placebo was not significant (P = 0.16). hsCRP fell compared with placebo [14].
- Population
- Non-diabetic adults with Kellgren grade 2 to 3 knee osteoarthritis, crossover [14].
- Sources
- [14]
- Caveats
- One trial.
Cyclic breast pain
Limited evidence: breast pain did not differ from placebo across 3 low-quality trials.
The numbers and sources
- Effect
- Across 3 trials, breast pain intensity did not differ between vitamin B6 and placebo (SMD -3.57, 95% CI -9.15 to 2.01) [6].
- Population
- Otherwise healthy women with breast pain, 3 placebo-controlled trials [6].
- Sources
- [6]
- Caveats
- The authors rated the certainty very low and the trials low quality. Heterogeneity was extreme (I² 99.56%) [6].
Therapies
Chronic pain across conditions
Shown to ease chronic pain about 0.5 standard deviations more than no acupuncture and about 0.2 more than sham acupuncture, with effects lasting a year.
Compared with sham acupuncture [2][3]; no acupuncture [2][3]
The numbers and sources
- Effect
- In individual patient data from 39 trials, acupuncture was superior to both sham and no acupuncture for each pain condition (all P < .001). The difference was close to 0.5 standard deviations against no acupuncture and close to 0.2 against sham, and about 15% of the effect was lost at 1 year. Effects were smaller in trials whose sham used a penetrating needle [2]. The earlier analysis of 29 trials found pain scores lower than sham by 0.23 SD for back and neck pain, 0.16 SD for osteoarthritis and 0.15 SD for chronic headache, and lower than no acupuncture by 0.55, 0.57 and 0.42 SD [3].
- Population
- 20,827 patients with nonspecific musculoskeletal pain, osteoarthritis, chronic headache or shoulder pain in 39 trials [2]. 17,922 patients in 29 trials [3].
- Sources
- [2], [3]
- Caveats
- The two analyses come from the same collaboration and the later one contains the earlier trials. Patients and acupuncturists cannot be blinded when the comparison is no acupuncture, so the larger effect includes expectation. The authors say factors beyond needling contribute to the effect [3].
Knee osteoarthritis, compared with no acupuncture or a waiting list
Shown to ease osteoarthritis pain 14.5 points on a 100-point scale more than a waiting list in the short term. One later trial found no gain at 1 year.
Compared with waiting list [8]; no acupuncture [3][9]
The numbers and sources
- Effect
- Against a waiting list, pain improved by 14.5 points more on a 100-point scale (SMD -0.96, 95% CI -1.19 to -0.72, 4 trials, 884 participants) and function by 13.0 points (SMD -0.89) [8]. Individual patient data put the difference from no acupuncture at 0.57 SD for osteoarthritis [3]. Against no acupuncture, needle acupuncture lowered knee pain by 1.1 units on a 0 to 10 scale at 12 weeks (95% CI -1.8 to -0.4), and not at 1 year [9].
- Population
- People with knee or hip osteoarthritis in 4 waiting-list trials [8]. 282 adults aged 50 or older [9].
- Sources
- [8], [3], [9]
- Caveats
- None of these comparisons could blind participants, so expectation and attention are part of the effect. The 1-point change at 12 weeks was below that trial's 1.8-unit threshold for clinical importance [9].
Chronic pain, compared with no treatment or usual care
Shown to ease chronic pain by a large amount against no treatment in the short term, and neck pain and fibromyalgia pain against no intervention or usual care.
Compared with no treatment [2]; no intervention [7]; usual care [6]
The numbers and sources
- Effect
- Against no treatment, cupping had a large short-term effect on pain (SMD -1.03, 95% CI -1.41 to -0.65) and a medium effect on disability (SMD -0.66) [2]. For neck pain, pain fell more than with no intervention (mean difference -2.42, 95% CI -3.98 to -0.86) and function improved [7]. In fibromyalgia, pain at day 18 was 12.4 points lower than with usual care (95% CI -18.9 to -5.9) [6].
- Population
- 1,172 people in 18 trials [2]. 18 trials of people with neck pain [7]. 141 patients with fibromyalgia [6].
- Sources
- [2], [7], [6]
- Caveats
- Without a sham, participants know they were treated. The same reviews and trials found no difference from sham cupping [2][6]. The neck pain reviewers rated the evidence low in quality [7].
Musculoskeletal pain, all comparisons pooled
Shown to ease musculoskeletal pain more than no treatment, sham needling and other therapies pooled together, from 72 hours to 24 weeks, in low-quality evidence.
Compared with no treatment, sham dry needling and other therapies, pooled together [3][4]
The numbers and sources
- Effect
- Across 42 trials, pain fell more than in the comparison groups within 72 hours (SMD -0.81, 95% CI -1.21 to -0.40), at 1 to 3 weeks (SMD -0.69, 95% CI -1.02 to -0.35), at 4 to 12 weeks (SMD -0.85, 95% CI -1.30 to -0.40) and at 13 to 24 weeks (SMD -0.81, 95% CI -1.64 to -0.03) [4]. An earlier review of 13 trials found less pain and higher pressure pain thresholds than control, sham or other treatment up to 12 weeks. At 6 to 12 months the difference in pain was not significant. Function improved against no treatment or sham, and did not differ from other physical therapy treatments [3].
- Population
- 42 trials of dry needling by physical therapists for musculoskeletal pain [4]. 13 trials of musculoskeletal pain conditions [3].
- Sources
- [3], [4]
- Caveats
- Both reviews pooled sham, no-treatment and other-treatment comparisons together, so the share of the effect beyond sham cannot be read from them. Heterogeneity downgraded the evidence to low quality at most time points [4], and the earlier review rated it very low to moderate [3]. The sham-controlled trials alone are in the next block.
Chronic pain
Shown to ease chronic pain moderately (Hedges' g -0.42) against control treatments, with larger effects after 8 or more sessions.
Compared with control interventions the source abstract does not describe [13]; standard care, and other psychological interventions [14]
The numbers and sources
- Effect
- In chronic musculoskeletal and nerve pain, hypnosis lowered pain intensity (Hedges' g -0.42 after treatment, -0.37 at short-term follow-up) and pain interference (-0.39). With 8 or more sessions the effect was g -0.555, and with fewer it was smaller and not significant [13]. An earlier meta-analysis found a moderate benefit over standard care, and a moderate benefit over other psychological treatments in people with pain other than headache [14].
- Population
- 530 adults in 9 trials [13]. Trials in chronic pain [14].
- Sources
- [13], [14]
- Caveats
- Heterogeneity across trials was large [14].
Low back pain, compared with a mix of sham, usual care, physiotherapy and no treatment
Shown to ease low back pain by about 13 points on a 100-point scale at 3 months, in pooled trials that mixed sham, usual care, physiotherapy and no-treatment comparisons.
Compared with sham treatment, usual medical care, physiotherapy and no treatment, pooled together [4]; control interventions the source abstract does not describe [5]; active treatment, placebo and no treatment [6]
The numbers and sources
- Effect
- At 3 months, pain fell 12.91 points more on a 100-point scale (95% CI -20.00 to -5.82) and function improved (SMD -0.36, 95% CI -0.58 to -0.14) in acute and chronic low back pain. In chronic low back pain alone, pain fell 14.93 points more (95% CI -25.18 to -4.68) [4]. A 2021 review of chronic low back pain found pain fell more than with control interventions (effect size -0.59, 95% CI -0.81 to -0.36) and function improved (-0.42) [5]. An earlier review found a smaller pain reduction (effect size -0.30, 95% CI -0.47 to -0.13) that held at short, intermediate and long-term follow-up [6].
- Population
- 15 trials, 10 in nonspecific low back pain [4]. 10 trials in chronic low back pain [5]. 6 trials with 8 comparisons [6].
- Sources
- [4], [5], [6]
- Caveats
- None of the trials in the 2021 review was judged at low risk of bias in every domain [5]. The comparisons could not be analyzed separately [4], so the pooled effect includes trials against no treatment, where patients knew they were untreated. The sham-only result is in the block above.
Chronic low back pain, compared with no treatment, usual care or placebo
Shown to ease chronic low back pain about 15 points on a 100-point scale against no treatment, usual care or placebo, with a smaller gain in function.
Compared with no treatment, usual care or placebo [2]; no-exercise true control [3]
The numbers and sources
- Effect
- Exercise lowered pain by 15.2 points on a 100-point scale at earliest follow-up (95% CI -18.3 to -12.2), a difference the reviewers called clinically important, and functional limitation by 6.8 points (95% CI -8.3 to -5.3), short of their clinical threshold [2]. In a network meta-analysis against true control, Pilates had the largest pain effect (SMD -1.86), and resistance and stabilization or motor control exercise the largest function effects (SMD -1.14 and -1.13). Stretching and McKenzie exercise did not differ from true control for pain or function [3].
- Population
- 249 trials of adults with chronic low back pain, mean age 43.7, 59% women [2]. 5,578 patients in 89 trials [3].
- Sources
- [2], [3]
- Caveats
- Most trials were at risk of performance bias because exercise cannot be blinded, and heterogeneity and publication bias lowered certainty [2]. The network meta-analysis rated its evidence low quality [3].
Chronic low back pain, compared with no treatment or usual care
Shown to ease chronic low back pain by about 20 points on a 100-point scale against no treatment. Against usual care the pain difference was smaller, about 10 points.
Compared with no treatment [4]; usual care [4]
The numbers and sources
- Effect
- Against no treatment, pain fell 20.32 points more on a 0 to 100 scale (95% CI -24.50 to -16.14, 4 trials, 366 participants) and back function improved (SMD -0.53, 95% CI -0.73 to -0.34, 5 trials, 2,960 participants), at moderate certainty. Against usual care, pain fell 10.26 points more (95% CI -17.11 to -3.40, 5 trials, 1,054 participants), which the reviewers did not count as clinically important, and function improved (SMD -0.47) [4].
- Population
- Adults with chronic nonspecific low back pain in 33 trials [4].
- Sources
- [4]
- Caveats
- Neither patients nor acupuncturists were blinded in these comparisons, so expectation is part of the effect. The effect was measured right after treatment [4].
Neck pain
Shown to ease neck pain slightly more than sham acupuncture in the short term, and more than a waiting list. The effect did not appear to last.
Compared with sham acupuncture [5]; inactive treatment [5]; waiting list [5]
The numbers and sources
- Effect
- For mechanical neck pain, pooled sham-controlled trials favored acupuncture in the short term (SMD -0.23, P = 0.0006). Acupuncture also eased pain more than inactive treatment, and pain and disability more than a waiting list, at short-term follow-up. The reviewers write that the effect does not seem sustainable over the long term [5].
- Population
- 27 trials of adults with whiplash, myofascial, arthritic, nonspecific, radicular or mechanical neck pain [5].
- Sources
- [5]
- Caveats
- Evidence was rated moderate in quality. Few trials were large, and repeated courses were not studied [5].
Period pain, compared with no treatment or NSAIDs
Shown in low-quality trials to ease period pain more than no treatment or NSAIDs, comparisons in which no one could be blinded.
Compared with no treatment [28][29]; NSAIDs [28][29]
The numbers and sources
- Effect
- Against NSAIDs, more women had pain relief with acupuncture (OR 4.99, 95% CI 2.82 to 8.82, 4 RCTs, 352 women), and adverse events were less common (OR 0.10, 95% CI 0.02 to 0.44, 4 RCTs, 239 women). Against no treatment, pain scores were lower with acupuncture in all 6 trials that reported them [28]. At 3 cycles after treatment, pain on a visual analogue scale was 47.80 points lower than with no intervention and 29.89 points lower than with NSAIDs [29].
- Population
- Women with primary dysmenorrhea in 42 RCTs [28]; 14 RCTs with 970 women [29].
- Sources
- [28], [29]
- Caveats
- Evidence was low quality, and 7 trials against NSAIDs were too heterogeneous to pool (I² 94%) [28]. The later review rated the evidence low certainty with high risk of bias [29]. Against sham, no difference was found (see above).
Chronic back pain
Shown to reduce chronic back pain intensity with a moderate effect (Hedges' g 0.60) that held over about 8 months, alone or added to other treatment.
Compared with control conditions the source abstract does not describe, with before-and-after studies included [10]
The numbers and sources
- Effect
- Biofeedback reduced pain intensity (g 0.60, 95% CI 0.44 to 0.76), and the effect held at an average 8-month follow-up (g 0.62). It also reduced depression (g 0.40), disability (g 0.49) and muscle tension (g 0.44). Effects held when only controlled studies were analyzed [10].
- Population
- 1,062 patients in 21 studies [10].
- Sources
- [10]
- Caveats
- The analysis included uncontrolled studies, and the abstract does not describe the controls [10].
Acute low back pain
Shown to ease acute low back pain by about 10 points on a 100-point scale and improve function modestly for up to 6 weeks, against sham or other treatments.
Compared with sham or alternative treatments [6]
The numbers and sources
- Effect
- Across 15 trials (1,711 patients), pain improved by 9.95 points on a 100-mm scale (95% CI -15.6 to -4.3). Across 12 trials (1,381 patients), function improved (effect size -0.39, 95% CI -0.71 to -0.07). Heterogeneity was not explained by who gave the manipulation or by type of manipulation [6].
- Population
- Adults with acute low back pain treated in ambulatory settings, 26 trials [6].
- Sources
- [6]
- Caveats
- The abstract pools sham and active comparisons together and calls heterogeneity large. Outcomes ran only to 6 weeks [6].
Neck pain
Shown to ease acute and subacute neck pain more than inactive controls in the short term with thoracic manipulation. Neck manipulation and mobilization gave similar results.
Compared with inactive controls [7]; mobilization [7]; certain medications [7]
The numbers and sources
- Effect
- Thoracic manipulation against inactive control improved pain at short-term follow-up (SMD -1.26, 95% CI -1.86 to -0.66, 5 trials, 346 participants) and function (SMD -1.40, 4 trials), at moderate quality. A single neck manipulation relieved pain immediately but not at short-term follow-up, at low to very low quality. Multiple sessions of neck manipulation produced similar results to mobilization, and better pain and function than certain medications in one trial of 182 people [7].
- Population
- 51 trials with 2,920 participants with neck pain [7].
- Sources
- [7]
- Caveats
- A funnel plot suggested publication bias for the thoracic manipulation results [7].
Chronic pain
Shown to ease chronic pain, disability and distress slightly more than usual treatment. Against other active treatments the benefit was very small and did not last.
Compared with treatment as usual [15]; active control treatments [15]
The numbers and sources
- Effect
- Against treatment as usual, CBT lowered pain (SMD -0.22, 95% CI -0.33 to -0.10, 29 trials), disability (SMD -0.32) and distress (SMD -0.34) at treatment end, effects largely maintained at follow-up. Against active controls, benefits were very small for pain (SMD -0.09, 95% CI -0.17 to -0.01, 23 trials), disability (SMD -0.12) and distress (SMD -0.09), and not maintained at follow-up [15].
- Population
- 59 CBT trials among 75 studies with 9,401 adults, mostly with fibromyalgia, chronic low back pain, rheumatoid arthritis or mixed chronic pain [15].
- Sources
- [15]
- Caveats
- Evidence quality ranged from moderate to low, and most trials were at high or unclear risk of bias. Headache was excluded [15].
Neck pain
Shown to ease neck pain in the short term against sham, placebo, waiting list or other needling pooled together. Neck function did not differ from physical or manual therapy.
Compared with sham, placebo, waiting list or another form of dry needling, pooled together [7]; manual therapy [7]; other physical therapy interventions [7]; sham dry needling, physical therapy or no treatment [8]
The numbers and sources
- Effect
- Against sham, placebo, waiting list or another form of dry needling, pain was lower immediately after treatment (mean difference -1.53 points, 95% CI -2.29 to -0.76) and in the short term (-2.31 points, 95% CI -3.64 to -0.99), and pain-related disability was lower in the short term (SMD -0.87). Against manual therapy, short-term pain was 0.51 points lower (95% CI -0.95 to -0.06) and disability did not differ. Against other physical therapy, no outcome differed. Nothing differed at mid-term, and neck range of motion did not change against any comparison [7]. In chronic nonspecific neck pain, function did not differ from control groups (mean difference 3.51, p = 0.14) and pain relief was borderline higher (mean difference 0.94, p = 0.05) [8].
- Population
- 28 trials of people with neck pain and trigger points [7]. 5 trials of chronic nonspecific neck pain [8].
- Sources
- [7], [8]
- Caveats
- Sham and waiting-list comparisons were pooled together, so the effect beyond sham is not separable. No trial could blind the therapist [7]. Evidence was rated low to moderate [7].
Low back pain
Shown to ease low back pain more than other treatments right after treatment in 11 trials. Effects on disability were smaller and effects at later follow-up unclear.
Compared with other treatments the review abstract does not list [9]; laser, physical therapy and other combined treatments [6]
The numbers and sources
- Effect
- Across 11 trials, dry needling of trigger points lowered pain intensity (SMD -1.06, 95% CI -1.77 to -0.36) and functional disability (SMD -0.76, 95% CI -1.46 to -0.06) more than other treatments after the intervention. Dry needling combined with other treatments lowered pain more than dry needling alone (SMD 0.83, 95% CI 0.55 to 1.11) [9]. A second review found results against laser, physical therapy and other combined treatments mixed, and called the evidence not robust enough for a firm conclusion [6].
- Population
- 802 people with low back pain and trigger points in 11 trials [9]. 16 trials of low back pain [6].
- Sources
- [9], [6]
- Caveats
- The reviewers call the effect on disability and at follow-up unclear [9]. Most trials were at high or unclear risk of bias [6].
Shoulder pain
Shown to ease nontraumatic shoulder pain by a small amount, about half a point, and disability by a larger amount, in the short term only.
Compared with comparison groups the review abstract does not describe [10]
The numbers and sources
- Effect
- Trigger point dry needling, alone or added to other treatment, lowered shoulder pain (mean difference -0.49 points, 95% CI -0.84 to -0.13, SMD -0.25) and pain-related disability (mean difference -9.99 points, 95% CI -15.97 to -4.01, SMD -1.14) more than the comparison groups. The effect on pain was found only in the short term [10].
- Population
- 6 trials of nontraumatic shoulder pain [10].
- Sources
- [10]
- Caveats
- Evidence was moderate in quality for pain and low for disability, downgraded for heterogeneity [10].
Tennis elbow
Shown to ease tennis elbow pain and disability with large effects in the short term, and grip strength with a small effect.
Compared with comparison groups the review abstract does not describe [15]
The numbers and sources
- Effect
- Dry needling, alone or with other treatment, lowered pain (SMD -1.13, 95% CI -1.64 to -0.62) and related disability (SMD -2.17, 95% CI -3.34 to -1.01), and raised pressure pain thresholds (SMD 0.98) and grip strength (SMD 0.48, 95% CI 0.16 to 0.81). The largest effects were in the short term [15].
- Population
- 320 people with lateral epicondylalgia in 7 trials [15].
- Sources
- [15]
- Caveats
- Evidence was low to moderate, downgraded for heterogeneity [15].
Endometriosis pain, compared with sham surgery
Shown to ease endometriosis pain in women more than a sham diagnostic laparoscopy in two small blinded trials, with 80% against 32% improved after excision.
Compared with diagnostic laparoscopy alone, with the women unaware of their group (sham surgery) [1][2][3][4]
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Six months after surgery, 16 of 20 women (80%) reported improvement after full excision and 6 of 19 (32%) after a diagnostic procedure only. Quality of life improved after excision and not after the sham. About 20% did not improve after surgery [1]. In a second trial, 62.5% improved or were free of symptoms 6 months after laser ablation, against 22.6% after diagnostic laparoscopy alone, rising to 73.7% when only mild and moderate disease was counted. Results were poorest for minimal disease [2]. At 1 year, relief continued in 90% of those who first responded [3]. The Cochrane review rated pooled pain data against diagnostic laparoscopy very low in certainty (MD 0.90 at 6 months and 1.65 at 12 months on a pain relief scale, 1 trial of 16 women), and quality of life did not differ (EQ-5D MD 0.03, 95% CI -0.12 to 0.18) [4].
- Population
- 39 women with endometriosis of all stages, crossover design [1]. 63 women with minimal to moderate endometriosis and pain [2][3]. 14 trials and 1,563 women in the review [4].
- Sources
- [1], [2], [3], [4]
- Caveats
- Both sham-controlled trials were small. The laser trial also cut the uterine nerves [2]. About 30% improved after the sham alone, a placebo response the authors found was not tied to disease severity [1]. The Cochrane review notes unclear blinding and poor reporting across trials [4].
Endometriomas: excision compared with drainage and ablation
Shown to lower pain and cyst recurrence in women with endometriomas against drainage and ablation. Endometriomas recurred in 5% to 17% after excision against 37% after ablation.
Compared with drainage and ablation of the cyst [10]
The numbers and sources
- Effect
- Up to two years after surgery, excision lowered the return of period pain (OR 0.25, 95% CI 0.12 to 0.52, 49% after ablation against 10% to 34% after excision) and of pain during sex (OR 0.09, 95% CI 0.03 to 0.22, 58% against 4% to 23%). At one year, endometriomas returned less often (OR 0.17, 95% CI 0.09 to 0.34) and fewer women needed more surgery (32% after ablation against 3% to 16%). Spontaneous pregnancy in the first year did not differ (OR 1.27, 95% CI 0.33 to 4.87) [10].
- Population
- 578 women of reproductive age with endometriomas of at least 3 cm in 9 trials [10].
- Sources
- [10]
- Caveats
- Low certainty, with no blinding and small numbers. No trial reported surgical complications other than conversion to open surgery [10].
Hormonal suppression after surgery, compared with none
Shown to lower endometriosis recurrence in women after conservative surgery when hormonal suppression followed, by about 59% against no treatment or placebo.
Compared with expectant management or placebo after surgery [13]
The numbers and sources
- Effect
- Recurrence, by imaging or return of symptoms at a median 18 months, was lower with hormonal suppression after surgery (RR 0.41, 95% CI 0.26 to 0.65, 14 studies, 1,766 patients, I² 68%). Pain scores were also lower (SMD -0.49, 95% CI -0.91 to -0.07). Results held for combined hormonal contraceptives and the levonorgestrel IUD, and in analyses limited to randomized trials [13].
- Population
- 2,137 premenopausal women who kept at least one ovary, in 13 randomized trials and 4 cohort studies [13].
- Sources
- [13]
- Caveats
- Heterogeneity was substantial. Suppression prevents pregnancy while it is used [13].
Pain in lab tests in healthy people
Shown to lower pain from lab pain tests in healthy volunteers (Hedges' g 0.54 to 0.76), mainly in people who respond strongly to suggestion.
Compared with no intervention [15]
The numbers and sources
- Effect
- Hypnosis lowered pain ratings and raised pain threshold and tolerance (g 0.54 to 0.76). With direct suggestions of pain relief, 42% of highly suggestible people and 29% of moderately suggestible people had clinically meaningful pain reductions, and people low in suggestibility gained little [15].
- Population
- 3,632 healthy participants in 85 mostly crossover trials using experimentally caused pain [15].
- Sources
- [15]
- Caveats
- Pain was induced in a lab, and the authors call for clinical data to show the effect carries over to chronic pain [15].
Pain across conditions
Shown to ease pain more than no treatment, by a large margin, and more than sham or active treatments, by smaller margins, in a meta-analysis of 67 trials.
Compared with sham treatments [2]; no treatment [2]; active treatments [2]
The numbers and sources
- Effect
- Massage lowered pain more than sham (SMD -0.44), no treatment (SMD -1.14) and active comparators (SMD -0.26) [2]. A map of 49 systematic reviews, 32 rated high quality, found their conclusions gave low strength of evidence for potential benefits in labor, shoulder, neck, low back, cancer, arthritis, postoperative and muscle soreness pain [3].
- Population
- 67 randomized trials of people with pain in the general population, 60 rated high quality [2]. 49 systematic reviews [3].
- Sources
- [2], [3]
- Caveats
- The evidence map notes few large, rigorous trials and poor description of the massage given, so reviews could not say which type helps which pain [3]. Participants cannot be blinded to massage.
Low back pain
Shown to ease subacute and chronic low back pain more than inactive controls in the short term, with no lasting difference. Against active treatments the pain difference was small.
Compared with inactive controls [4]; active treatments [4]; usual care [5]
The numbers and sources
- Effect
- For subacute and chronic low back pain, massage lowered pain more than inactive controls in the short term (SMD -0.75, 95% CI -0.90 to -0.60, 7 trials, 761 participants) and improved function (SMD -0.72), with no difference in the long term. Against active controls, pain was lower in the short term (SMD -0.37, 12 trials, 964 participants) and long term (SMD -0.40), and function did not differ [4]. In 401 adults, Roland disability scores at 10 weeks were 2.9 points lower with relaxation massage and 2.5 points lower with structural massage than with usual care [5].
- Population
- 25 trials with 3,096 participants, almost all with subacute or chronic low back pain [4]. 401 adults aged 20 to 65 with chronic low back pain in Seattle [5].
- Sources
- [4], [5]
- Caveats
- The reviewers rated the evidence low to very low and wrote that they have very little confidence in massage for low back pain [4]. The trial did not blind participants to massage versus usual care [5].
Herniated lumbar disc, injection into the disc
Shown in pooled trials to give higher treatment success than steroid injections and more pain relief than medications at 6 months or more, with results similar to microdiscectomy.
Compared with steroid injections [5]; conventional medications [5]; microdiscectomy [5]
The numbers and sources
- Effect
- At 6 months, treatment success was higher than with steroid injections (OR 3.95, 95% CI 2.44 to 6.39). Pain fell more than with conventional medications at 6 months (SMD 1.65, 95% CI 1.08 to 2.22) and 12 months (SMD 1.52). At 18 months, pain did not differ from microdiscectomy (SMD -0.05, 95% CI -0.67 to 0.57) [5].
- Population
- People with herniated lumbar discs in trials searched to January 2024 [5].
- Sources
- [5]
- Caveats
- None of these comparisons was against a sham injection, so participants knew which treatment they had. A separate 2025 meta-analysis on disc injections of ozone has been retracted and is not used here.
Knee osteoarthritis, compared with no exercise
Shown to ease knee osteoarthritis pain about 12 points on a 100-point scale and improve function about 10 points against no exercise, right after treatment.
Compared with non-exercise or no-treatment control groups [4]
The numbers and sources
- Effect
- Exercise reduced pain (SMD -0.49, 44 trials, 3,537 participants), equal to 12 points on a 0 to 100 scale, and improved physical function by 10 points (SMD -0.52), both immediately after treatment. Quality of life improved by 4 points. Two to six months after treatment ended, pain was 6 points lower and function 3 points better [4].
- Population
- 54 trials of people with knee osteoarthritis [4].
- Sources
- [4]
- Caveats
- Only 4 trials blinded participants, and pain and function were self-reported [4].
Hip osteoarthritis, compared with no exercise
Shown to ease hip osteoarthritis pain and improve function about 8 and 7 points on a 100-point scale against no exercise, sustained 3 to 6 months later.
Compared with non-exercise control groups [5]
The numbers and sources
- Effect
- Exercise reduced pain (SMD -0.38, 9 trials, 549 participants), equal to 8 points on a 0 to 100 scale, and improved function by 7 points, with a number needed to treat of 6 for both. The pain reduction held 3 to 6 months after supervised treatment ended. Quality of life did not change (3 small studies) [5].
- Population
- 10 trials of people with hip osteoarthritis [5].
- Sources
- [5]
- Caveats
- No trial could blind participants, and outcomes were self-reported [5].
Knee osteoarthritis, compared with hyaluronic acid
Shown in pooled trials to give better knee pain, function and WOMAC scores after injection than hyaluronic acid injections.
Compared with hyaluronic acid injections [5]
The numbers and sources
- Effect
- Across 27 randomized trials, scores after injection were better with PRP than with hyaluronic acid for WOMAC (P < .001), pain on the visual analog scale (P < .01) and the Subjective IKDC knee score (P < .001) [5].
- Population
- 1,042 patients given PRP and 1,128 given hyaluronic acid, mean age 57.7 and 59.0, mean follow-up about 14 months [5].
- Sources
- [5]
- Caveats
- Hyaluronic acid is an active injection, not a placebo. The abstract gives P values without effect sizes [5].
Pain and anxiety in labor
Shown to lower labor pain by about 1.9 points on a 0 to 10 scale and reduce anxiety, against placebo, usual care or no intervention.
Compared with placebo, usual care or no intervention [13]
The numbers and sources
- Effect
- Foot reflexology lowered pain (mean difference -1.89 on a 0 to 10 scale, 95% CI -2.34 to -1.45) and anxiety (SMD -0.88, 95% CI -1.41 to -0.34), shortened the stages of labor and raised birth satisfaction. It lowered pulse and breathing rate and did not change blood pressure. The reviewers rated the evidence moderate for pain [13].
- Population
- 1,189 pregnant women in 13 trials [13].
- Sources
- [13]
- Caveats
- Heterogeneity was very high (I² 92% for pain). Some trials had high risk of bias in how women were assigned to groups [13].
Knee osteoarthritis, other comparisons
Limited evidence: pooled small trials found less osteoarthritis pain and better function in the short term, with no difference at medium or long term.
Compared with non-drug treatments, sham techniques or no added treatment, pooled together [13]; control, sham or placebo treatment [14]
The numbers and sources
- Effect
- Across 7 trials, dry needling lowered pain (SMD -0.76, 95% CI -1.24 to -0.29, I² 74%) and improved physical function (SMD -0.98, 95% CI -1.54 to -0.42, I² 75%) in the short term, with no difference at medium or long term [13]. A review of 9 trials found contradictory results for trigger point needling. Periosteal stimulation improved pain and function right after treatment, and intramuscular electrical stimulation lowered pain with marked heterogeneity [14].
- Population
- 291 people with hip or knee osteoarthritis in 7 trials [13]. 9 trials of knee osteoarthritis [14].
- Sources
- [13], [14]
- Caveats
- Evidence was rated very low quality for risk of bias, heterogeneity and imprecision [13]. Sham and no-treatment comparisons were pooled together.
Hysterectomy compared with excision alone
Linked to fewer repeat operations and more pain relief than excision alone in women, in observational studies. By 7 years, 77% to 92% avoided reoperation, against 45%.
Compared with laparoscopic excision with the uterus and ovaries kept [11][12]; hysterectomy with and without removal of the ovaries, against each other [11][12]
The numbers and sources
- Effect
- At 2, 5 and 7 years, 79.4%, 53.3% and 44.6% of women had avoided further surgery after excision alone, against 95.7%, 86.6% and 77.0% after hysterectomy keeping the ovaries and 96.0%, 91.7% and 91.7% after hysterectomy with the ovaries removed. In women aged 30 to 39, removing the ovaries did not significantly lengthen surgery-free time [11]. At 24 months, against excision alone, hysterectomy keeping the ovaries improved pain outside periods by 1.41 more points out of 10, pain during sex by 1.12, back pain by 1.29 and quality of life by 8.77 out of 100. With the ovaries removed, the gains were 2.22, 1.05, 1.18 and 12.41 [12].
- Population
- 240 women at one US clinic, 120 per group [11]. Women having surgery for rectovaginal endometriosis at 86 specialist endometriosis centers, 2009 to 2021 [12].
- Sources
- [11], [12]
- Caveats
- Neither study was randomized, so women chosen for hysterectomy may differ from others. The second study's oophorectomy result was sensitive to loss to follow-up [12]. Hysterectomy ends the ability to carry a pregnancy, and removing both ovaries brings on menopause.
Fibromyalgia
Limited evidence: four small trials found lower pain and fewer tender points than placebo, results the review authors call preliminary.
Compared with placebo [19]
The numbers and sources
- Effect
- Against placebo, homeopathy lowered tender point count (SMD -0.42, 95% CI -0.78 to -0.05), pain intensity (SMD -0.54, 95% CI -0.97 to -0.10) and fatigue (SMD -0.47, 95% CI -0.90 to -0.05) [19].
- Population
- 4 randomized trials, plus case reports and observational studies [19].
- Sources
- [19]
- Caveats
- Few small trials. The authors write that any conclusions are preliminary [19].
Pain and side effects of breast surgery
One trial of 200 women found a 15-minute hypnosis session before breast surgery lowered pain at discharge from 48 to 22 on a 100-point scale against empathic listening.
Compared with nondirective empathic listening as an attention control [16]
The numbers and sources
- Effect
- Women given hypnosis needed less propofol and lidocaine during surgery and reported less pain (22.43 against 47.83 on a 100-point scale), nausea, fatigue, discomfort and emotional upset at discharge. Use of fentanyl, midazolam and recovery room pain medicine did not differ [16].
- Population
- 200 women having breast biopsy or lumpectomy, mean age 48.5 [16].
- Sources
- [16]
- Caveats
- One trial. Patients knew which group they were in [16].
Knee osteoarthritis
One trial of 222 adults found weekly massage improved knee osteoarthritis scores more than light touch or usual care at 8 weeks, with no difference at 52 weeks.
Compared with light touch [7]; usual care [7]
The numbers and sources
- Effect
- At 8 weeks, WOMAC global scores improved by 8.16 points more than light touch (95% CI -13.50 to -2.81) and 9.55 points more than usual care (95% CI -14.66 to -4.45), with gains in pain, stiffness and function. At 52 weeks, change did not differ across groups (P = 0.707) [7].
- Population
- 222 adults with knee osteoarthritis [7].
- Sources
- [7]
- Caveats
- One trial. Light touch was the closest thing to a sham, and participants knew which hands-on treatment they had.
Low back pain and herniated disc, compared with sham injections
Two small double-blind trials found ozone injections beside the spine eased back pain and disability more than injections of oxygen or very dilute ozone.
Compared with paraspinal injections of pure oxygen [2]; paravertebral injections of very dilute ozone, 0.1 µg/mL [3]
The numbers and sources
- Effect
- In chronic discogenic low back pain, pain on the visual analog scale fell 5.6 points with ozone and 2.4 with pure oxygen, and the Oswestry disability score fell 19.07 and 7.8 points (P < 0.001), with exercise in both groups [2]. In acute lumbar disc herniation, pain and disability scores were lower with ozone than with placebo at 15 and 30 days and one month after treatment ended (P < 0.05), added to conservative treatment [3].
- Population
- 30 adults with MRI-confirmed chronic discogenic low back pain [2]. 38 adults with acute lumbar disc herniation [3].
- Sources
- [2], [3]
- Caveats
- Two small single-center trials with follow-up of 3 months or less. Pure oxygen and dilute ozone are injected gases themselves, so neither control is inert.
Knee osteoarthritis, compared with placebo
Limited evidence: one double-blind trial and three reviews found less knee osteoarthritis pain than placebo, and an umbrella review rated every review critically low in confidence.
Compared with placebo injections [6][7]
The numbers and sources
- Effect
- After 8 weeks of injections, pain was 2.16 points lower than placebo on the visual analog scale (95% CI 0.42 to 3.89), and the Lequesne index, WOMAC scores and several quality of life scores improved more. The Timed Up and Go test did not differ [6]. An umbrella review of 8 reviews covering 15 trials found 3 reporting significant pain reduction against placebo, while 5 found ozone no better than other therapies, with less consistent effects on joint function [7].
- Population
- 98 adults with symptomatic knee osteoarthritis in Brazil [6]. 8 systematic reviews of 15 trials with 3,685 patients [7].
- Sources
- [6], [7]
- Caveats
- All 8 reviews had critically low confidence ratings on AMSTAR 2 [7]. The placebo trial lasted 8 weeks [6].
Knee osteoarthritis, compared with a steroid injection
One trial of 156 adults found less knee pain and disability at 1 year with physical therapy than with a glucocorticoid injection.
Compared with intra-articular glucocorticoid injection [8]
The numbers and sources
- Effect
- At 1 year, WOMAC scores (0 to 240) were 37.0 with physical therapy and 55.8 with injection, a difference of 18.8 points (95% CI 5.0 to 32.6) [8].
- Population
- 156 patients with knee osteoarthritis, mean age 56, in the US Military Health System [8].
- Sources
- [8]
- Caveats
- One trial, without blinding of participants.
Knee osteoarthritis, compared with sham acupuncture
Mixed results: pooled trials found a small edge over sham acupuncture that reviewers judged below clinical relevance, and a 282-person trial found no difference from sham.
Compared with sham acupuncture [3][8][9][10]; sham laser [9]
The numbers and sources
- Effect
- Against sham, pain improved by 0.9 points more on a 20-point scale (SMD -0.28, 95% CI -0.45 to -0.11, 9 trials, 1,835 participants), below the reviewers' 1.3-point threshold for clinical relevance. With the shams most likely to blind participants, the benefit was smaller and not significant, and at 6 months it was borderline (SMD -0.10) [8]. Individual patient data put the edge over sham at 0.16 SD for osteoarthritis [3]. In people over 50 with chronic knee pain, needle acupuncture did not differ from sham for pain (-0.4 units on a 0 to 10 scale, 95% CI -1.2 to 0.4) or function at 12 weeks [9]. In a 480-person trial, 60.3% responded to electroacupuncture, 58.6% to manual acupuncture and 47.3% to sham at 8 weeks. Electroacupuncture differed from sham (P = 0.0234) and manual acupuncture narrowly did not (P = 0.0507) [10].
- Population
- 16 trials with 3,498 people with knee or hip osteoarthritis [8]. 282 adults aged 50 or older in Australia [9]. 480 adults in China [10].
- Sources
- [8], [3], [9], [10]
- Caveats
- Heterogeneity was substantial across sham-controlled trials [8]. The trials used different shams, from non-penetrating needles to inactive lasers.
Chronic low back pain, compared with other treatments
Shown to relieve chronic low back pain about as much as other guideline-endorsed treatments, with a small gain in function and a pain edge too small to matter clinically.
Compared with other therapies that guidelines endorse [3]; therapies that guidelines do not endorse [3]; other interventions [4]
The numbers and sources
- Effect
- Against other guideline-endorsed therapies, short-term pain did not differ (mean difference -3.17 on a 100-point scale, 95% CI -7.85 to 1.51) and function improved slightly (SMD -0.25, 95% CI -0.41 to -0.09). Against therapies guidelines do not endorse, pain fell 7.48 points more (95% CI -11.50 to -3.47), which the reviewers did not count as clinically better, and function improved (SMD -0.41). Results were similar at intermediate and long-term follow-up [3]. An earlier Cochrane review found a small, not clinically relevant, short-term effect on pain (mean difference -4.16, 95% CI -6.97 to -1.36) and function (SMD -0.22) against other interventions [4].
- Population
- 47 trials with 9,211 adults, mostly aged 35 to 60 [3]. 26 trials with 6,070 participants [4].
- Sources
- [3], [4]
- Caveats
- The two reviews come from overlapping author groups and share trials. Heterogeneity could not be explained [3].
Chronic low back pain, compared with sham acupuncture
Mixed results: pain eased slightly more than with sham acupuncture right after treatment, a difference below the clinically important threshold, and back function did not differ.
Compared with sham acupuncture [4]
The numbers and sources
- Effect
- Against sham, acupuncture lowered pain by 9.22 points on a 0 to 100 scale in the immediate term (95% CI -13.82 to -4.61, 7 trials, 1,403 participants), short of the 15-point threshold the reviewers set as clinically important. Back-specific function did not differ from sham (SMD -0.16, 95% CI -0.38 to 0.06, 5 trials, 1,481 participants), and short-term quality of life did not differ by a clinically meaningful amount (SMD 0.24) [4].
- Population
- 33 trials with 8,270 adults with chronic nonspecific low back pain, two thirds of them in 7 German trials [4].
- Sources
- [4]
- Caveats
- Certainty was rated low to very low for these comparisons, mostly because acupuncturists could not be blinded [4].
Endometriosis pain
Mixed results: reviews of mostly unblinded trials found less endometriosis pain with acupuncture, while a sham-controlled trial found period pain eased during treatment but not 12 weeks later.
Compared with placebo, traditional Chinese medicine and Western medicine [30]; medications and herbs, and placebo in one pilot trial [31]; sham acupuncture [32]; a comparison the source abstract does not describe [33]
The numbers and sources
- Effect
- Across 14 studies (793 patients), pain severity fell more with acupuncture than with control treatments (SMD -1.10, 95% CI -1.45 to -0.75) [30]. Across 10 studies, pain fell 1.36 points more on a 0 to 10 scale (95% CI 1.01 to 1.72) [31]. In a sham-controlled trial of 12 weeks of treatment, period pain fell more with acupuncture by the end of treatment but not by week 24, pain lasted fewer days, and pelvic pain outside periods and pain with sex did not differ. Adverse events did not differ [32]. A Cochrane review found one trial (67 women) meeting its criteria, with lower period pain scores in the acupuncture group (MD -4.81 points) [33].
- Population
- 793 patients in 14 studies [30]; 10 studies of 8 to 36 patients per arm [31]; 106 women aged 20 to 40 with endometriosis pain at 4 hospitals in China [32]; 67 women [33].
- Sources
- [30], [31], [32], [33]
- Caveats
- Only one pilot trial in [31] used a placebo control, and the rest could not be blinded. The authors of [30] point to design and quality flaws in the trials.
Chronic low back pain, compared with sham manipulation
Mixed results: one small meta-analysis found manipulation eased low back pain more than sham, and two larger reviews rated the sham evidence too weak to settle.
Compared with sham manipulation [3][4][5]; inert interventions [4]
The numbers and sources
- Effect
- In 4 trials pooled against sham, symptoms improved more with manipulation (SMD -0.36, 95% CI -0.59 to -0.12) [5]. A review of 47 trials rated the evidence against sham low to very low in quality and called its effects uncertain [3]. An earlier Cochrane review found very low-quality evidence that manipulation was not significantly better than inert interventions or sham for short-term pain or function [4].
- Population
- 9 trials, 4 pooled, in nonspecific low back pain [5]. 9,211 adults [3]. 6,070 participants [4].
- Sources
- [5], [3], [4]
- Caveats
- The practitioner cannot be blinded, several sham trials were small, and some had high dropout [5].
Chronic pain, compared with other active treatments
Mixed results: one meta-analysis found no pain difference from other active treatments, while reviews of neck and low back pain trials found cupping ahead.
Compared with other active treatments [2][7]; medication [8]; usual care [8]
The numbers and sources
- Effect
- Against other active treatments, chronic pain did not differ significantly (SMD -0.24, 95% CI -0.57 to 0.09), while disability was lower (SMD -0.52) [2]. In neck pain trials, pain fell more than with active controls (p = 0.0009) [7]. In low back pain trials, pain fell more than with medication (d 1.8, 8 trials) and usual care (d 1.07, 5 trials) at 2 to 8 weeks, with no difference at 1 month or 3 to 6 months [8].
- Population
- 18 trials [2]. 18 neck pain trials [7]. 921 participants in 11 low back pain trials [8].
- Sources
- [2], [7], [8]
- Caveats
- Heterogeneity was high across the low back pain subgroups [8].
Musculoskeletal pain, compared with sham needling
Mixed results: in adequately blinded trials, pain did not differ from sham needling. Less well blinded sham trials favored dry needling, as did two small low back pain trials.
Compared with sham dry needling, penetrating or non-penetrating [5]; sham needling [6]
The numbers and sources
- Effect
- Across 24 sham-controlled trials, the 3 adequately blinded comparisons found no difference in short-term pain (SMD -0.40, 95% CI -0.96 to 0.15, 122 participants), and the 4 adequately blinded comparisons at 1 to 6 months found none in long-term pain (SMD -0.30, 95% CI -0.62 to 0.02, 202 participants). Inadequately blinded comparisons favored dry needling in the short term (SMD -0.71, 95% CI -1.05 to -0.38, 504 participants) and the long term (SMD -1.14, 95% CI -1.64 to -0.65, 284 participants). The one adequately blinded comparison measured right after treatment, in 31 people, favored dry needling (SMD -0.76) [5]. In low back pain, 2 sham-controlled trials favored dry needling for pain after treatment (SMD -2.74, 95% CI -3.77 to -1.71) and at follow-up (SMD -1.05, 95% CI -1.70 to -0.40), and disability at follow-up did not differ [6].
- Population
- 24 trials comparing dry needling with a sham that simulated it, searched to February 2016 [5]. 2 sham-controlled trials within 16 low back pain trials [6].
- Sources
- [5], [6]
- Caveats
- 19 of the 24 trials were at high or unclear risk of bias, and no trial tried to blind the therapist. The reviewers say the subgroups were small and the results are uncertain [5]. Most low back pain trials were at high or unclear risk of bias [6].
Low back pain, compared with acupuncture
Mixed results: low back pain eased more than with acupuncture right after treatment in 6 trials, and pain and disability did not differ at follow-up.
Compared with acupuncture, including wrist-ankle acupuncture in one trial [6]
The numbers and sources
- Effect
- Across 6 trials with 467 participants, pain intensity after treatment was lower with dry needling than with acupuncture (SMD -0.96, 95% CI -1.80 to -0.12). At follow-up, pain and disability did not differ. In one trial of 60 people with acute low back pain, one 5-minute session lowered pain more than wrist-ankle acupuncture [6].
- Population
- 467 people with low back pain in 6 trials [6].
- Sources
- [6]
- Caveats
- Most trials were at high or unclear risk of bias, and the reviewers say the evidence is not robust [6].
Stomach pain and irritable bowel syndrome in children
Mixed results: pooled trials found more children treated successfully than with no intervention, while a primary care trial found no difference in relief at 12 months.
Compared with no intervention [9]; care as usual [10]
The numbers and sources
- Effect
- Hypnotherapy led to treatment success more often than no intervention (RR 2.86, 95% CI 1.19 to 6.83, number needed to treat 5), at low certainty [9]. In 152 children aged 7 to 17 treated in primary care, home-based guided hypnotherapy added to usual care did not change adequate relief at 12 months (79.5% against 74.3%, adjusted OR 1.47). More children had relief at 3 months (adjusted OR 2.74) and 6 months (4.26) [10].
- Population
- 91 children in 2 trials of hypnotherapy against no intervention [9]. 152 children in Dutch primary care [10].
- Sources
- [9], [10]
- Caveats
- The pooled result rests on two small trials at risk of bias [9]. Relief was high in both groups by 12 months [10].
Labor pain
Mixed results: women taught hypnosis used pain medication less often, and satisfaction with pain relief, coping and spontaneous birth did not differ from control groups.
Compared with standard care, supportive counseling and relaxation training [17]
The numbers and sources
- Effect
- Women in the hypnosis groups were less likely to use pain medication (RR 0.73, 95% CI 0.57 to 0.94, 8 trials, 2,916 women), with no difference in epidural use, sense of coping (MD 0.22) or spontaneous vaginal birth (RR 1.12). Against standard care or relaxation, primary outcomes did not differ. Against supportive counseling, pain medication use was lower (RR 0.48, 95% CI 0.32 to 0.73, 2 trials) [17].
- Population
- 2,954 women in 9 trials [17].
- Sources
- [17]
- Caveats
- Evidence for the main comparison was rated low quality, with heterogeneity that could not be explained [17].
Lymphedema after breast cancer, compared with no drainage
Mixed results: in one review, drainage added 7% more swelling reduction to compression bandaging, while two later meta-analyses found no significant reduction in arm volume.
Compared with compression bandaging alone [1]; standard physiotherapy alone [1]; control groups without drainage [3][4]
The numbers and sources
- Effect
- Added to compression bandaging, drainage gave an additional 7.11% reduction in swelling (95% CI 1.75% to 12.47%, 2 trials, 83 participants), and added to standard physiotherapy it did not differ. Pain and heaviness eased in both groups with no difference between them [1]. A later review found no significant effect on volume or quality of life, and lower pain (SMD -0.72, 95% CI -1.34 to -0.09) [3]. Another found no significant reduction in lymphedema (SMD -0.09, 95% CI -0.85 to 0.67, 8 trials, 338 patients) [4].
- Population
- 6 trials of 24 to 45 women each [1]. 1,564 patients in 11 trials [3]. 338 patients in 8 trials [4].
- Sources
- [1], [3], [4]
- Caveats
- Trials were small, and in four of the Cochrane trials the person measuring swelling knew the treatment [1]. None of these comparisons used placebo drainage.
Low back pain, compared with sham treatment
Mixed results: a 2024 review of sham-controlled trials found no difference in back or neck pain, while the largest trial found more people improved with treatment than with sham.
Compared with sham or placebo interventions [2]; sham osteopathic treatment [3]
The numbers and sources
- Effect
- Pooled against sham or placebo, osteopathic treatment did not change pain intensity (SMD -0.15, 95% CI -0.38 to 0.08, 7 trials, 1,173 patients) or disability (SMD -0.09, 95% CI -0.25 to 0.08, 6 trials, 1,153 patients) in neck or low back pain, and most of the 9 trials found no difference [2]. In the largest trial, people given osteopathic treatment were more likely than those given sham to have a 30% or greater drop in chronic low back pain at 12 weeks (response ratio 1.38, 95% CI 1.16 to 1.64) and a 50% or greater drop (1.41, 95% CI 1.13 to 1.76), a medium effect by Cochrane Back Review Group criteria. Back function, general health and work disability did not differ from sham [3].
- Population
- 9 trials of adults with neck or low back pain [2]. 455 adults with chronic nonspecific low back pain [3].
- Sources
- [2], [3]
- Caveats
- The 2024 review pooled neck and back pain and rated the certainty moderate to very low [2]. The practitioner cannot be blinded to giving real or sham treatment.
Low back pain in pregnancy and after childbirth
Mixed results: a review found less pain in pregnant and postpartum women, while the largest pregnancy trial found treatment no different from placebo ultrasound, with both better than usual care.
Compared with usual care only, and usual care plus placebo ultrasound [7]; control groups the source abstract does not describe [8]
The numbers and sources
- Effect
- In pregnancy, pain fell 16.65 points more (on a 100-point scale) and function improved (SMD -0.50), at moderate quality. After childbirth, pain fell 38.00 points more and function improved (SMD -2.12), at low quality [8]. In 400 women in the third trimester, 7 treatments over 9 weeks eased pain and slowed loss of back function more than usual care alone (P < .001), and results with osteopathic treatment were similar to placebo ultrasound [7].
- Population
- 5 trials in pregnancy and 3 after childbirth [8]. 400 women in their third trimester [7].
- Sources
- [8], [7]
- Caveats
- The trial authors suggest the placebo ultrasound may have been more active than intended [7].
Headache, irritable bowel syndrome and other conditions
Mixed results: an overview of 27 reviews found possible relief in migraine and irritable bowel syndrome, and no relief in acute low back pain, fibromyalgia or other headaches.
Compared with no treatment, sham treatment or other non-osteopathic treatment [16]
The numbers and sources
- Effect
- Osteopathic treatment may relieve symptoms in adults with migraine and irritable bowel syndrome. It did not appear to relieve acute nonspecific low back pain, fibromyalgia, headaches of various causes, lower urinary tract symptoms in women, or cerebral palsy in children. Evidence for vertigo, COPD, high blood pressure and gynecological complaints was insufficient [16]. An earlier overview rated the evidence for children's conditions, headache and irritable bowel syndrome limited and inconclusive [17].
- Population
- 27 systematic reviews covering nine indications [16]. 9 reviews with 55 trials and 3,740 participants [17].
- Sources
- [16], [17]
- Caveats
- Included reviews were rated low or critically low in quality [17], and the trials were heterogeneous and partly of poor quality [16].
Low back pain, compared with usual care and other treatments
Mixed results: pooled trials found a small function gain at one month against usual care, no lasting pain difference, and no difference in excellent or poor outcomes.
Compared with usual care and other treatments the review abstract does not list [4]
The numbers and sources
- Effect
- Across 9 studies, disability on the Oswestry index favored ozone overall (SMD -0.28, 95% CI -0.51 to -0.06), at one month only, with no difference at 2 weeks or 6 months. Pain favored ozone overall by a small amount (SMD -0.12, 95% CI -0.24 to -0.01), and subgroup and sensitivity analyses found no difference. Excellent outcomes (OR 0.95, 95% CI 0.54 to 1.67) and poor outcomes (OR 1.25, 95% CI 0.66 to 2.37) did not differ [4].
- Population
- 1,711 participants with low back pain in 9 studies [4].
- Sources
- [4]
- Caveats
- The reviewers describe the benefit over usual care as limited and the results as inconsistent [4].
Joint and muscle pain, compared with corticosteroid injections
Mixed results: across musculoskeletal conditions, steroid injections eased pain more in the short term, while in knee osteoarthritis alone ozone eased pain more.
Compared with corticosteroid injections [8][9]
The numbers and sources
- Effect
- Across 11 studies of musculoskeletal pain of several kinds, short-term pain fell more with corticosteroid injections (d 0.31, 95% CI 0.01 to 0.60), and medium-term pain did not differ (d -0.17, 95% CI -0.42 to 0.07) [8]. In 7 knee osteoarthritis trials, ozone injections reduced pain more than corticosteroid injections in the short and medium term and improved function in the medium term [9].
- Population
- 534 people with musculoskeletal pain in 11 studies [8]. 409 people with knee osteoarthritis in 7 trials [9].
- Sources
- [8], [9]
- Caveats
- Both reviews describe the included trials as limited in quality [8][9]. The knee review abstract gives no effect sizes [9].
Chronic low back pain, compared with other treatments
Mixed results: exercise eased pain about 9 points on a 100-point scale more than other conservative treatments, below the clinical threshold, and did not differ from manual therapy.
Compared with other conservative treatments [2]; education alone [2]; non-exercise physical therapy [2]; manual therapy [2]
The numbers and sources
- Effect
- Against all other conservative treatments, pain fell 9.1 points more (95% CI -12.6 to -5.6) and functional limitation 4.1 points more, neither meeting the reviewers' threshold for clinical importance. By subgroup, pain fell more than with education alone (-12.2) and non-exercise physical therapy (-10.4), and did not differ from manual therapy (1.0, 95% CI -3.1 to 5.1) [2].
- Population
- 249 trials of adults with chronic low back pain [2].
- Sources
- [2]
- Caveats
- Low-certainty evidence for these comparisons [2].
Compared with surgery
Mixed results: trials found outcomes similar to surgery for degenerative meniscus tears, spinal stenosis and ACL tears, and smaller gains than knee replacement.
Compared with arthroscopic partial meniscectomy [9]; surgical decompression [10]; early ACL reconstruction [11]; total knee replacement followed by nonsurgical treatment [12]
The numbers and sources
- Effect
- For degenerative meniscus tears, knee scores at 2 years differed by 0.9 points between 12 weeks of supervised exercise and surgery (95% CI -4.3 to 6.1), and 19% of the exercise group crossed over to surgery [9]. For lumbar spinal stenosis, physical function improved by 19.2 points with physical therapy and 22.4 with surgery, with no difference at 2 years, and 57% crossed over from therapy to surgery [10]. For acute ACL tears, knee scores rose 39.4 points with rehabilitation plus optional later reconstruction and 39.2 with rehabilitation plus early reconstruction, and 36 of 59 never had surgery [11]. For knee osteoarthritis, knee replacement plus nonsurgical treatment improved scores by 32.5 points against 16.0 with nonsurgical treatment alone, and had more serious adverse events (24 against 6) [12].
- Population
- 140 adults aged 35 to 60 with degenerative meniscal tears [9]. 169 surgical candidates aged 50 or older with lumbar spinal stenosis [10]. 121 young, active adults with acute ACL tears [11]. 100 patients eligible for knee replacement [12].
- Sources
- [9], [10], [11], [12]
- Caveats
- Each condition rests on one trial, and crossover to surgery was common [9][10]. The spinal stenosis trial had no untreated group [10].
Knee osteoarthritis, compared with saline placebo
Mixed results: pooled placebo-controlled trials found less knee pain up to 6 months, while the largest trial, of 288 people, found no difference from saline at 12 months.
Compared with saline placebo injections [2][3][4]
The numbers and sources
- Effect
- In 288 adults aged 50 or older, knee pain changed by -2.1 points with PRP and -1.8 with saline at 12 months (difference -0.4, 95% CI -0.9 to 0.2, on a 0 to 10 scale with a clinically important difference of 1.8). Cartilage volume did not differ, and 29 of 31 secondary outcomes did not differ [2]. Across 11 trials, pain was lower than placebo at 3 months (MD -1.1, 95% CI -1.8 to -0.4) and 6 months (MD -2.0, 95% CI -2.8 to -1.2), and not at 12 months. WOMAC scores improved at 3 months only [3]. A review of 20 placebo-controlled studies found better function and pain at 6 and 12 months, at very low certainty [4].
- Population
- 288 adults with mild to moderate medial knee osteoarthritis in Australia [2]. 1,616 patients in 11 trials, mean age 56.9 [3]. 1,774 PRP and 1,518 placebo participants in 20 studies [4].
- Sources
- [2], [3], [4]
- Caveats
- Heterogeneity was high in the pooled pain results [3], and certainty very low [4]. The largest trial, blinded for participants, injectors and assessors, found no difference [2].
Rotator cuff tendinopathy, injection
Mixed results: a pooled review reported short-term pain relief against placebo and corticosteroids, while a placebo-controlled trial found no difference from saline at one year.
Compared with placebo or corticosteroid injections [10]; saline injection, both groups exercising [11]
The numbers and sources
- Effect
- Across 30 randomized trials, PRP reduced pain and improved function in the short term against placebo and corticosteroids, with no greater benefit beyond 12 months [10]. In 40 patients, WORC, SPADI and pain scores did not differ from saline at any time point through one year (P = .174, .314 and .904 at one year), and both groups improved [11].
- Population
- About 2,500 participants in 30 trials [10]. 40 adults aged 18 to 70 with chronic rotator cuff tendinopathy [11].
- Sources
- [10], [11]
- Caveats
- The review abstract gives no effect sizes and does not separate placebo from corticosteroid comparisons [10].
Pain, compared with controls pooled together
Mixed results: a meta-analysis of four trials reported less pain with Reiki, though its interval included no effect, and a review of biofield therapies rated pain evidence strong.
Compared with control groups the source abstract does not describe [9]; control conditions in 66 studies of biofield therapies, which the abstract does not describe [10]
The numbers and sources
- Effect
- Across 4 trials, pain scores after the last session were lower with Reiki (SMD -0.927, 95% CI -1.867 to 0.0124), an interval that crosses zero although the author reported a significant decrease [9]. A best-evidence synthesis of Reiki, therapeutic touch and healing touch rated the evidence strong for reducing pain intensity in pain populations and moderate in hospitalized and cancer populations [10].
- Population
- 212 participants in 4 randomized trials [9]. 66 clinical studies of biofield therapies [10].
- Sources
- [9], [10]
- Caveats
- The synthesis rated study quality medium overall and did not separate sham from other comparisons in its abstract [10].
Neck pain
Limited evidence: very low-quality trials suggested some massage techniques improved function and tenderness more than control or placebo, and reviewers called the effect uncertain.
Compared with control or placebo treatment [6]; education [6]
The numbers and sources
- Effect
- Very low-quality evidence suggested traditional Chinese massage and strain-counterstrain techniques may improve function and tenderness more than control or placebo, and massage may ease pain bothersomeness more than education in the short term. Most trials measured outcomes immediately after treatment [6].
- Population
- 15 trials of adults with mechanical neck disorders [6].
- Sources
- [6]
- Caveats
- All trials were rated low or very low in quality, and only 4 of 15 described the massage adequately. The reviewers made no recommendation [6].
Neck pain
Limited evidence: four small trials pooled against no treatment or sham found less neck pain, at very low quality, and a 2024 sham-only review found no difference.
Compared with no intervention or sham treatment, pooled together [9]; sham or placebo interventions [2]
The numbers and sources
- Effect
- Against no intervention or sham, osteopathic treatment lowered pain (effect size -1.57, 95% CI -2.50 to -0.65) and improved function (-1.71), with very low quality evidence for every outcome [9]. The 2024 review, which pooled neck and low back pain against sham or placebo only, found no difference in pain or disability [2].
- Population
- 5 trials, 4 pooled, of adults with nonspecific neck pain [9]. 9 trials in neck or low back pain [2].
- Sources
- [9], [2]
- Caveats
- None of the neck pain trials was judged at low risk of bias in every domain [9].
Pain, compared with sham Reiki
Mixed results: a fibromyalgia trial found Reiki no different from sham given by actors, and a knee pain trial found more people improved with Reiki than with sham.
Compared with sham Reiki given by actors, with or without touch [7]; sham Reiki and a waiting list [8]
The numbers and sources
- Effect
- In 100 adults with fibromyalgia treated twice weekly for 8 weeks, pain and every secondary outcome were nearly identical whether a Reiki master or an actor gave the treatment, with touch or at a distance [7]. In 164 adults with knee osteoarthritis, symptoms improved more with Reiki than with a waiting list (P = .02), and a reduction of more than 30% was reported by 55% given Reiki, 20% given sham Reiki and 13% on the waiting list [8].
- Population
- 100 adults with fibromyalgia in Seattle [7]. 164 adults with knee osteoarthritis [8].
- Sources
- [7], [8]
- Caveats
- The knee trial abstract does not report a direct test of Reiki against sham [8].
Excision compared with ablation
Not shown to differ: excision and ablation eased pain from superficial endometriosis in women by similar amounts at 12 months, in two reviews.
Compared with ablation of the lesions [4][5][6][7]
The numbers and sources
- Effect
- Pooled across 3 trials, reductions in period pain (MD -0.03, 95% CI -1.27 to 1.22), pain with bowel movements (MD 0.46, 95% CI -1.09 to 2.02) and pain during sex (MD 0.10, 95% CI -2.36 to 2.56) did not differ at 12 months, nor did scores beyond 12 months [5]. Overall pain at 12 months did not differ in the Cochrane review (MD 0.00, 95% CI -1.22 to 1.22, 1 trial, 103 women) [4]. A blinded trial found no difference in overall pain at 12 months [6]. In a robot-assisted trial, the only difference was in pain during sex at 6 months, which favored ablation [7].
- Population
- 346 women with minimal to mild endometriosis in 4 trials [5]. 103 women [4]. Women with pelvic pain and visible endometriosis [6]. 73 women with minimal to mild endometriosis [7].
- Sources
- [5], [4], [6], [7]
- Caveats
- These trials covered superficial, minimal to mild disease, not deep endometriosis. The reviewers call for larger trials with longer follow-up [5].
Period pain, compared with sham acupuncture
Not shown to ease period pain more than sham acupuncture in women with primary dysmenorrhea. The one trial at low risk of bias found no difference.
Compared with sham or placebo acupuncture [28][29]
The numbers and sources
- Effect
- Against sham or placebo, findings across 6 trials were inconsistent, and the only trial at low risk of bias in every domain found no difference at 3, 6 or 12 months [28]. A 2025 review of 14 trials found acupuncture did not ease pain more than sham at 3 cycles after treatment [29].
- Population
- 42 RCTs with 4,640 women with moderate to severe primary dysmenorrhea, 6 of them sham-controlled [28]; 14 RCTs with 970 women [29].
- Sources
- [28], [29]
- Caveats
- The Cochrane authors rated the evidence low quality, from risk of bias, poor reporting, inconsistency and possible publication bias. No sham-controlled trial reported adverse events [28].
Chronic pain, compared with sham cupping
Not shown to ease chronic pain more than sham cupping, in two meta-analyses and three later trials of back pain, knee osteoarthritis and fibromyalgia.
Compared with sham cupping [2][3][4][5][6]
The numbers and sources
- Effect
- Against sham cupping, pain did not differ significantly (SMD -0.27, 95% CI -0.58 to 0.05) and neither did disability (SMD -0.26) [2]. In 5 trials of dry against placebo cupping, the short-term pain difference was -9.9 points on a 100-point scale (95% CI -30.5 to 10.7), very uncertain at every time point [3]. In 90 people with chronic low back pain, pain differed by 0.0 to 0.6 points on a 0 to 10 scale over 8 weeks [4]. In 62 women with knee osteoarthritis, no outcome differed from sham at any time point [5]. In 141 people with fibromyalgia, pain at day 18 differed from sham by -3.0 points (95% CI -9.9 to 3.9) [6].
- Population
- 1,172 people with chronic pain in 18 trials [2]. 281 adults with musculoskeletal complaints in 5 trials [3]. 90 adults [4]. 62 women aged 50 to 75 [5]. 141 patients, 139 of them women [6].
- Sources
- [2], [3], [4], [5], [6]
- Caveats
- Few sham-controlled trials exist and most are small. The second meta-analysis rated certainty very low and four of its trials at high risk of bias [3].
Bruising, swelling and pain after surgery or injury, arnica
Not shown to differ from placebo in a 1998 review of 8 trials. A 2021 meta-analysis found a small edge over placebo that fell short of statistical significance.
Compared with placebo [17][18]; active comparators and no treatment [18]
The numbers and sources
- Effect
- Eight placebo-controlled trials, most in tissue trauma and most with severe methodological flaws, did not suggest homeopathic arnica worked better than placebo [17]. In 18 placebo-controlled comparisons after surgery, the pooled effect was Hedges' g 0.18 (95% CI -0.007 to 0.373, P = 0.059). Active-comparator trials gave g 0.26 with high heterogeneity, an effect driven by nonrandomized studies that moved toward zero in randomized trials [18].
- Population
- 8 trials [17]. 23 publications with 28 comparisons in surgical patients [18].
- Sources
- [17], [18]
- Caveats
- The 2021 authors read their result as a small effect, though the placebo-controlled interval included zero [18].
Tennis elbow
Not shown to ease tennis elbow pain or function more than placebo injection at 3, 6 or 12 months, for PRP or whole-blood injections, in a Cochrane review.
Compared with placebo injection [6]
The numbers and sources
- Effect
- At 3 months, mean pain was 3.7 out of 10 with placebo and 0.16 points better with autologous blood or PRP (95% CI 0.60 better to 0.29 worse, 8 studies, 523 participants). Function was 1.86 points better on a 100-point scale (95% CI 4.9 better to 1.25 worse), and treatment success was 67% against 65% (RR 1.00, 95% CI 0.83 to 1.19). No clinically important benefit appeared at 6 or 12 months [6].
- Population
- 32 trials with 2,337 people with lateral elbow pain, 10 of them placebo-controlled [6].
- Sources
- [6]
- Caveats
- Evidence was moderate in certainty, downgraded for bias [6].
Achilles tendinopathy
Not shown to improve chronic Achilles tendinopathy more than a sham or saline injection, in three placebo-controlled trials through one year.
Compared with sham injection, a dry needle under the skin not entering the tendon [7]; saline injection, both groups doing eccentric exercises [8][9]
The numbers and sources
- Effect
- At 6 months, VISA-A scores were 54.4 with PRP and 53.4 with sham (adjusted difference -2.7, 95% CI -8.8 to 3.3, clinically important difference 12) [7]. With eccentric exercise, VISA-A improved 21.7 points with PRP and 20.5 with saline at 24 weeks (difference -0.9, 95% CI -12.4 to 10.6) [8]. At one year the difference was 5.5 points (95% CI -4.9 to 15.8), and 59% in both groups were satisfied [9].
- Population
- 240 adults at 24 UK sites, mean age 52 [7]. 54 adults aged 18 to 70 in the Netherlands, followed for 24 weeks [8] and one year [9].
- Sources
- [7], [8], [9]
- Caveats
- The two smaller reports are the same trial at two time points [8][9].
Pain, compared with sham reflexology or plain foot massage
Not shown to ease pain more than sham reflexology or plain foot massage in three trials, in multiple sclerosis, Parkinson's disease and advanced breast cancer.
Compared with sham reflexology [4]; sham massage [5]; lay foot manipulation, and conventional care [6]
The numbers and sources
- Effect
- In 73 people with multiple sclerosis, pain fell by a median of 50% in both the reflexology and sham reflexology groups over 10 weeks, and reflexology was not superior to sham [4]. In 30 people with Parkinson's disease and chronic pain, pain fell 12.3 mm on a 100-mm scale with reflexology and 17.9 mm with sham massage, with no difference between groups (P = 0.88) [5]. In 385 women with advanced breast cancer, pain did not differ between reflexology, lay foot manipulation and conventional care [6].
- Population
- 73 people with multiple sclerosis [4]. 30 adults with Parkinson's disease in France [5]. 385 women with advanced breast cancer at 13 US oncology clinics [6].
- Sources
- [4], [5], [6]
- Caveats
- Pain improved substantially in both arms of the sham-controlled trials, so touch and attention may account for much of the effect [4][5].
Knee osteoarthritis, compared with sham needling
Small trials found adding dry needling to exercise did not ease knee osteoarthritis pain or disability more than sham dry needling, through one year.
Compared with sham dry needling, both groups exercising [11][12]
The numbers and sources
- Effect
- At one year, pain differed from sham by 0.32 points (95% CI -1.12 to 1.18, P = 0.92) and WOMAC score by 0.29 points (95% CI -6.16 to 6.74). Both groups improved over time. In the dry needling group 90.3% reduced their medication, against 26.3% with sham [11]. In a 20-person pilot, pain and WOMAC scores improved in both groups with no group difference [12].
- Population
- 62 adults with knee osteoarthritis in a multicenter trial [11]. 20 adults aged 65 or older with thigh trigger points [12].
- Sources
- [11], [12]
- Caveats
- Two small trials from the same group, both adding needling to exercise.
Fibromyalgia, Myers' cocktail
One small trial found weekly Myers' cocktail drips did not differ from a saline-type drip on any fibromyalgia measure at 8 or 16 weeks.
Compared with weekly infusions of lactated Ringer's solution [4]
The numbers and sources
- Effect
- No outcome differed between groups at 8 or 16 weeks: tender points, global pain, physical function, depression or quality of life. Both groups improved from baseline. The Myers' cocktail group improved in tender points, pain, depression and quality of life, and the placebo group in tender points only. One minor adverse event occurred in the treatment group [4].
- Population
- 34 adults with fibromyalgia in Connecticut, treated weekly for 8 weeks [4].
- Sources
- [4]
- Caveats
- A pilot study. The authors note a high placebo response and a sample too small to show a difference [4].
Hip and knee osteoarthritis, compared with sham treatment
Two small trials found physical therapy programs did not ease hip or knee osteoarthritis pain more than sham ultrasound with inert gel.
Compared with sham ultrasound and inert gel [6][7]
The numbers and sources
- Effect
- In hip osteoarthritis, pain at week 13 fell from 58.8 to 40.1 mm with physical therapy and from 58.0 to 35.2 mm with sham, a difference of 6.9 mm favoring sham (95% CI -3.9 to 17.7). Function did not differ [6]. In knee osteoarthritis, pain fell by 2.2 cm with physiotherapy and 2.0 cm with placebo at 12 weeks, and global improvement was reported by 70% and 72% [7].
- Population
- 102 adults with painful hip osteoarthritis [6]. 140 adults with knee osteoarthritis, 119 completing [7].
- Sources
- [6], [7]
- Caveats
- The sham involved regular contact with a therapist, so both groups received attention. The authors of [7] wrote that the program did no more than regular contact with a therapist.
Teething pain in infants
Not studied in people. Homeopathic teething tablets and gels were sold in the US for infant teething, and no trial of them was located.
No study in people. This rests on documented traditional use.
The numbers and sources
- Effect
- Homeopathic teething tablets containing belladonna were marketed for infants in the US until the FDA requested a recall of the largest brand in 2017 [2][20]. A search of Europe PMC for trials of homeopathic teething products found none.
- Population
- No study population. Products sold for infants [20].
- Sources
- [2], [20]
- Caveats
- Marketing a product for teething says nothing about whether it relieves teething pain. The risk record for these products is under Risks.
Practices
Period pain, compared with no treatment
Shown to ease period pain in women against no treatment, by about 1.9 cm on a 10 cm scale over 3 months of use, in pooled trials of low certainty.
Compared with no treatment [3][4]
The numbers and sources
- Effect
- Across 25 trials (2,393 women), pain after 3 months was lower with heat than with no treatment (WMD -1.85 cm, 95% CI -2.29 to -1.41). Within 24 hours of a painful period, the difference was larger (WMD -3.52 cm, 95% CI -5.01 to -2.02, 3 trials, 248 women) [3]. An earlier review found one trial of 132 women in which heat lowered pain against no treatment (MD -4.04, 95% CI -4.88 to -3.20) [4].
- Population
- 5,359 women with primary dysmenorrhea in 57 trials [3]. 6 trials [4].
- Sources
- [3], [4]
- Caveats
- Women knew whether they were using heat, so expectation can add to the effect. The reviewers judged the evidence low in certainty and write that heat "may" reduce pain [3]. The earlier review's comparison rests on one trial [4].
Period pain, compared with pain medicines
Shown to ease period pain in women as much as, or slightly more than, NSAIDs or acetaminophen, in two reviews of trials.
Compared with NSAIDs [3]; pain medicines [4]; ibuprofen 400 mg three times a day [5]; acetaminophen 1,000 mg [6]
The numbers and sources
- Effect
- After 3 months, pain was slightly lower with heat than with NSAIDs (WMD -1.10 cm, 95% CI -1.51 to -0.70, 22 trials, 1,938 women), and within 24 hours (WMD -1.50 cm, 95% CI -2.86 to -0.15, 2 trials, 167 women) [3]. Against pain medicines, heating pads lowered pain (SMD -0.72, 95% CI -0.97 to -0.48, 2 trials, 274 women) [4]. Heat with a placebo pill gave mean relief of 3.27 against 3.07 for ibuprofen with an unheated patch. Adding heat to ibuprofen did not raise relief (P = .096) but shortened the time to noticeable relief from 2.79 to 1.5 hours [5]. Against acetaminophen 1,000 mg, a heat wrap gave more relief over 8 hours (2.48 against 2.17, p = 0.015) and less cramping [6].
- Population
- Women with primary dysmenorrhea in 22 trials [3] and 2 trials [4]. 81 women [5]. 344 women [6].
- Sources
- [3], [4], [5], [6]
- Caveats
- The pooled certainty was low [3]. The single-day acetaminophen trial blinded only the investigator [6].
Chronic pain
Shown to ease chronic pain slightly in pooled trials rated low in quality. In back pain, an 8-week course matched CBT and beat usual care.
Compared with treatment as usual, passive controls, and education or support groups [8]; active control programs [3]; usual care and cognitive behavioral therapy [9]
The numbers and sources
- Effect
- Across 30 trials, pain fell more with mindfulness meditation than with controls (SMD 0.32, 95% CI 0.09 to 0.54), smaller in trials rated fair or higher in quality (SMD 0.19, 95% CI 0.03 to 0.34, 19 trials) [8]. Against active controls, pain improved by an effect size of 0.33 (95% CI 0.03 to 0.62) [3]. In 342 adults with chronic low back pain, clinically meaningful improvement in function at 26 weeks reached 60.5% with mindfulness-based stress reduction, 57.7% with CBT and 44.1% with usual care (relative risk against usual care 1.37, 95% CI 1.06 to 1.77, and against CBT 0.95) [9].
- Population
- 3,536 adults with chronic pain from migraine, headache, back pain, osteoarthritis or nerve pain in 38 trials [8]. 342 adults aged 20 to 70 with chronic low back pain [9].
- Sources
- [8], [3], [9]
- Caveats
- Heterogeneity was substantial (I² 77.6%) and evidence for pain was rated low quality [8]. The back pain course included gentle yoga as well as meditation [9].
Knee osteoarthritis pain
Shown to reduce knee osteoarthritis pain compared with placebo, by about 14 mm on a 100 mm scale in one meta-analysis. A later review rated certainty very low.
The numbers and sources
- Effect
- Across 22 placebo-controlled trials (1,063 participants), low-level laser reduced pain by 14.23 mm on a 100 mm visual analogue scale at the end of therapy (95% CI 7.31 to 21.14) and by 15.92 mm at follow-ups 1 to 12 weeks later (95% CI 6.47 to 25.37). At the doses advised by the World Association for Laser Therapy, the reduction was 18.71 mm. Disability was also reduced [6]. Across 10 placebo-controlled studies (542 participants), pain at rest was lower with photobiomodulation (-0.7, 95% CI -1.1 to -0.2), and the Timed Up and Go test did not differ [7].
- Population
- 1,063 people with knee osteoarthritis in 22 trials [6]. 542 people in 10 trials [7].
- Sources
- [6], [7]
- Caveats
- The later review judged every study at unclear to high risk of bias and the certainty of evidence very low [7]. The first review states that major knee osteoarthritis treatment guidelines do not endorse low-level laser [6]. These trials used clinic lasers applied to the joint, not consumer light panels.
Period pain, compared with an unheated patch
Shown to ease period pain in women more than an unheated placebo patch, in two trials. Mean pain relief over 2 days was 3.27 with heat against 1.95 without.
Compared with an unheated patch with a placebo pill (sham) [4][5]
The numbers and sources
- Effect
- Over 2 days, mean pain relief scores were 3.27 with a heated patch and placebo pill, 3.07 with an unheated patch and ibuprofen, 3.55 with both, and 1.95 with an unheated patch and placebo pill (all P ≤ .001 against the sham) [5]. A review found two trials favoring heat over unheated placebo therapy [4].
- Population
- 84 women, 81 completing, in a double-dummy trial [5]. 6 trials [4].
- Sources
- [5], [4]
- Caveats
- A heated and an unheated patch feel different, so the blinding may be imperfect. The trials are small.
Acute low back pain, compared with an oral placebo
Shown to ease acute and subacute low back pain slightly against an oral placebo after 5 days, by about 1 point on a 0 to 5 scale, in two trials.
Compared with oral placebo [7]; a comparison the abstract does not describe, for a heated blanket [7]
The numbers and sources
- Effect
- In two trials of 258 people, a heat wrap reduced pain after five days against oral placebo (WMD 1.06, 95% CI 0.68 to 1.45, on a 0 to 5 scale). In one trial of 90 people, a heated blanket reduced acute pain immediately after use (WMD -32.20, 95% CI -38.69 to -25.71, on a 0 to 100 scale). There was not enough evidence to judge cold, and conflicting evidence on heat against cold [7].
- Population
- 1,117 people in 9 trials, most with acute or subacute low back pain [7].
- Sources
- [7]
- Caveats
- The reviewers call the evidence moderate for a small short-term effect, from few trials. No pooled trial covered chronic low back pain [7].
Muscle soreness after exercise
Shown to ease muscle soreness after exercise when applied within an hour, in pooled trials, with hot packs ranking highest in a network analysis.
Compared with control groups the abstract does not describe [10]; passive recovery and other cold and heat methods [11]
The numbers and sources
- Effect
- Heat lowered soreness within 24 hours (SMD -1.17, as reported with a 95% CI of -2.62 to -0.09) and after 24 hours (SMD -0.82, 95% CI -1.38 to -0.26). Hot packs lowered it within 24 hours (SMD -2.31) and after (SMD -1.78), while other heat methods did not differ from control. Heat and cold did not differ from each other (P = 0.16) [10]. In a network analysis of ten methods, hot packs ranked first for pain relief at 24 and 48 hours [11].
- Population
- 1,098 people in 32 trials [10]. 1,367 people in 59 trials [11].
- Sources
- [10], [11]
- Caveats
- Both reviews come from the same group and note limited trial quality [10][11].
Fibromyalgia pain
Shown to reduce pain in people with fibromyalgia in one meta-analysis of 9 small studies. Adverse events occurred in 23.8% of treated patients.
The numbers and sources
- Effect
- Across 9 studies (288 patients), hyperbaric oxygen reduced pain compared with control (SMD -1.56, 95% CI -2.18 to -0.93, I² 51%). Most studies also reported better tender points, fatigue, function and sleep disturbance. Adverse events occurred in 44 of 185 patients (23.8%), and 12 (6.5%) withdrew because of them [7].
- Population
- 288 people with fibromyalgia in 9 randomized and non-randomized controlled trials [7].
- Sources
- [7]
- Caveats
- The pooled studies include non-randomized trials, and the abstract does not say how many used a sham. No serious adverse events were observed.
Neck pain
Shown to reduce chronic neck pain by about 20 mm on a 100 mm scale compared with placebo, lasting up to 22 weeks after treatment, in one meta-analysis.
The numbers and sources
- Effect
- Across 16 RCTs (820 patients), pain intensity fell 19.86 mm on a 100 mm visual analogue scale (95% CI 10.04 to 29.68) in 11 trials. In 7 trials with follow-up of 1 to 22 weeks, the reduction was 22.07 mm (95% CI 17.42 to 26.72). In chronic neck pain, the relative risk of improvement was 4.05 (95% CI 2.74 to 5.98) [8].
- Population
- 820 patients with acute or chronic neck pain in 16 trials [8].
- Sources
- [8]
- Caveats
- One meta-analysis, published in 2009, of clinic laser treatment applied to painful sites.
Tendon pain and plantar fasciitis
Shown to reduce pain in lower-limb tendinopathy and plantar fasciitis by about 13 mm on a 100 mm scale in one meta-analysis, with wide intervals.
The numbers and sources
- Effect
- Across randomized trials, low-level laser reduced pain by 13.15 mm on a 100 mm scale at the end of therapy (95% CI 7.82 to 18.48) and 12.56 mm at 4 to 12 weeks (95% CI 5.69 to 19.42). Disability improved (SMD 0.39, 95% CI 0.09 to 0.7). Added to exercise at the doses advised by the World Association for Laser Therapy, it reduced pain 18.15 mm more than exercise alone [9].
- Population
- People with lower extremity tendinopathy or plantar fasciitis in 18 trials, 10 of them against placebo [9].
- Sources
- [9]
- Caveats
- The authors note wide confidence intervals, no large trials and no long-term data [9].
Fibromyalgia
Shown to improve fibromyalgia symptom, pain and fatigue scores compared with placebo laser in one meta-analysis. It added nothing to an exercise program.
The numbers and sources
- Effect
- Across 9 RCTs (325 patients), low-level laser improved Fibromyalgia Impact Questionnaire scores (SMD 1.16, 95% CI 0.64 to 1.69), pain severity (SMD 1.18, 95% CI 0.82 to 1.54), tender points, fatigue, stiffness, depression and anxiety more than placebo laser. Laser plus a standardized exercise program gave no extra symptom relief over exercise alone [10].
- Population
- 325 people with fibromyalgia in 9 RCTs [10].
- Sources
- [10]
- Caveats
- One meta-analysis of small trials.
Knee osteoarthritis, against no program or attention control
Shown to ease knee osteoarthritis pain and stiffness and improve function in one meta-analysis of 16 trials. A small trial found more relief than wellness education and stretching.
Compared with control groups the source abstract does not describe [8]; wellness education and stretching, as an attention control [9]
The numbers and sources
- Effect
- Tai chi improved pain (SMD -0.69, 95% CI -0.95 to -0.44), stiffness (SMD -0.59), physical function (SMD -0.92, 95% CI -1.16 to -0.69), dynamic balance (SMD 0.69) and physical and mental quality of life [8]. In 40 adults, WOMAC pain improved more with tai chi than with the attention control at 12 weeks (mean difference -118.80 mm, 95% CI -183.66 to -53.94), along with function, chair stand time and depression scores [9].
- Population
- 986 patients with knee osteoarthritis in 16 trials [8]. 40 adults with symptomatic knee osteoarthritis, mean age 65 [9].
- Sources
- [8], [9]
- Caveats
- Strength of evidence for the main outcomes was low or moderate [8]. Patients knew their group [9].
Period pain, compared with sham or no treatment pooled together
Shown to ease period pain in women by 1.39 points with high-frequency and 2.04 with low-frequency TENS, against sham or no treatment pooled together, at low certainty.
Compared with placebo TENS or no treatment, pooled together [5]
The numbers and sources
- Effect
- High-frequency TENS lowered pain against placebo or no treatment (MD -1.39, 95% CI -2.51 to -0.28, 10 trials, 345 women, I² 88%), as did low-frequency TENS (MD -2.04, 95% CI -2.95 to -1.14, 3 trials, I² 0%). High- and low-frequency TENS did not clearly differ (MD 0.89, 95% CI -0.19 to 1.96) [5].
- Population
- 585 women aged 12 to 49 with primary dysmenorrhea in 20 trials [5].
- Sources
- [5]
- Caveats
- The Cochrane review pools placebo and no-treatment arms, so blinded and unblinded comparisons are mixed. Certainty was downgraded for risk of bias [5].
Pain in many conditions, compared with placebo TENS
Shown to lower pain during or right after use against placebo TENS in adults with many kinds of pain, across 91 trials, at moderate certainty.
Compared with placebo TENS [8]; sham TENS [9]
The numbers and sources
- Effect
- Pain was lower during or immediately after TENS than with placebo (SMD -0.96, 95% CI -1.14 to -0.78, 91 trials, 4,841 people), and acute or chronic pain, diagnosis and risk of bias did not change the effect [8]. An overview of Cochrane reviews of chronic pain found one review with lower pain against sham (MD -1.58, 95% CI -2.08 to -1.09 on a 0 to 10 scale, 5 trials, 207 people), and rated all its evidence very low in quality [9].
- Population
- 24,532 adults with pain in 381 trials [8]. 2,895 people in 51 trials across 8 Cochrane reviews [9].
- Sources
- [8], [9]
- Caveats
- Most trials were small, and effects were measured during or right after a session. The overview found too little usable data to report on lasting relief or daily function [9].
Pain in many conditions, compared with usual treatments
Shown to lower pain during or right after use more than medicines or other usual treatments, across 61 trials in adults, at low certainty.
Compared with drug and non-drug treatments used as standard care [8]
Fibromyalgia pain with movement
Shown to lower pain with movement in women with fibromyalgia, by 1.0 point against placebo TENS and 1.8 points against no TENS, out of 10.
Compared with placebo TENS [12]; no TENS [12]; physical therapy alone [13]
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- After 4 weeks of home use during activity, pain with movement fell more with TENS than with placebo TENS (MD -1.0, 95% CI -1.8 to -0.2) or no TENS (MD -1.8, 95% CI -2.6 to -1.0), and fatigue with movement fell too. Global improvement was reported by 70% on TENS, 31% on placebo TENS and 9% with no TENS [12]. In a trial across 28 physical therapy clinics, adding TENS lowered pain with movement at day 60 (MD -1.2, 95% CI -1.6 to -0.7), and 41% against 13% had a reduction of 30% or more. At 180 days, 81% found TENS helpful [13].
- Population
- 301 women with fibromyalgia on stable medicines [12]. 384 adults with fibromyalgia, 91% female [13].
- Sources
- [12], [13]
- Caveats
- The larger trial randomized clinics, not people, and had no placebo device [13].
Chronic low back pain, against no exercise
Shown to improve back function and pain slightly against no exercise in a Cochrane review, by amounts below the thresholds the reviewers set as clinically important.
Compared with waiting list, usual care or education [1]; a self-care book [2]; an educational book and newsletters [3]
The numbers and sources
- Effect
- At 3 months, back function improved 1.69 points on the 24-point Roland-Morris scale (95% CI -2.73 to -0.65, 11 trials, 1,155 participants, minimal clinically important difference 5 points) and pain fell 4.53 points on a 0 to 100 scale (95% CI -6.61 to -2.46, 9 trials, clinically important difference 15 points). More people rated their back pain improved or resolved (risk ratio 2.33, 95% CI 1.46 to 3.71) [1]. In 228 adults, function at 12 weeks was 2.5 points better with 12 yoga classes than with a self-care book (95% CI -3.7 to -1.3), and still 1.8 points better at 26 weeks [2]. In 320 mostly low-income adults, yoga was not superior to an educational book for function or pain at 12 weeks, and 21 percentage points fewer yoga participants used pain medication [3].
- Population
- 2,223 adults in 21 trials, mostly women in their 40s or 50s [1]. 228 primary care patients [2]. 320 racially diverse adults at a safety-net hospital and 7 health centers [3].
- Sources
- [1], [2], [3]
- Caveats
- Every trial was at high risk of performance and detection bias, and no trial compared yoga with sham yoga. The reviewers judged it unlikely that blinded comparisons would find a clinically important benefit [1].
Period pain
Shown in one meta-analysis of 4 small trials to lower period pain more than no yoga in women with primary dysmenorrhea, with a wide margin of uncertainty.
Compared with not doing yoga [19]
The numbers and sources
- Effect
- Across 4 trials, a yoga program lowered period pain more than no yoga (SMD -2.09, 95% CI -3.99 to -0.19) [19].
- Population
- 230 women with primary dysmenorrhea, 129 doing yoga and 101 not [19].
- Sources
- [19]
- Caveats
- Four small trials, with a confidence interval that runs from a very large to a small effect. No trial compared yoga with another exercise [19].
Pain
Limited evidence: two small studies reported less pain while grounded, one in 16 massage therapists compared with ungrounded weeks and one uncontrolled study of 12 adults.
Compared with weeks without grounding, in the same people [3]; before grounding, in the same people [2]
The numbers and sources
- Effect
- In a stepped wedge design, massage therapists reported significant decreases in pain, fatigue, tiredness and depressed mood and increases in physical function and energy while grounded at work and during sleep, compared with weeks not grounded [3]. Self-reported pain was reduced or eliminated in nearly all of 12 adults who slept grounded for 8 weeks [2].
- Population
- 16 massage therapists, mean age 42.8, at one wellness center in California [3]. 12 adults [2].
- Sources
- [3], [2]
- Caveats
- Sixteen and 12 people. The massage therapist trial was led by an author who, in another paper, disclosed work as a contractor for the company that sponsors grounding research [3][4]. Outcomes were self-reported.
Acute low back pain, compared with ibuprofen and acetaminophen
One trial found a heat wrap eased acute low back pain more than ibuprofen 1,200 mg or acetaminophen 4,000 mg a day, on day 1 and days 3 to 4.
Compared with ibuprofen and acetaminophen [8]
The numbers and sources
- Effect
- Day 1 pain relief averaged 2 with the heat wrap, 1.51 with ibuprofen and 1.32 with acetaminophen. Relief on days 3 to 4 averaged 2.61, 1.68 and 1.95. Trunk flexibility and disability also improved more with heat [8].
- Population
- 371 adults with acute nonspecific low back pain, 113 on heat, 106 on ibuprofen and 113 on acetaminophen [8].
- Sources
- [8]
- Caveats
- Only the investigator was blinded, and the placebo and unheated-wrap groups (20 and 19 people) were there for blinding, not for comparison [8].
Acute low back pain, heat with exercise
One trial found a heat wrap plus exercise restored function in 72% of people with acute low back pain, against about 20% with heat, exercise or a booklet alone.
Compared with an education booklet [9]; exercise alone [9]; a heat wrap alone [9]
The numbers and sources
- Effect
- Two days after 5 days of treatment, 72% of the heat plus exercise group had returned to pre-injury function, against 20% with heat alone, 20% with exercise alone and 19% with the booklet. Function improved 175% more than with the booklet [9]. A Cochrane review reports the same finding of added benefit from exercise [7].
- Population
- 100 adults, mean age 31, with low back pain of less than 3 months [9].
- Sources
- [9], [7]
- Caveats
- One small trial with about 25 people per group [9].
Chronic pain
One study found 77% of chronic pain patients given daily far-infrared sessions alongside usual treatment had returned to work at 2 years, against 50% without the sessions.
The numbers and sources
- Effect
- Pain scores, pain behavior, depression and anger scores fell in both groups after 4 weeks of inpatient treatment. With added thermal therapy, anger scores were lower (p = 0.05) and pain behavior slightly lower (p = 0.07). Two years after discharge, 17 of 22 patients (77%) in the thermal group had returned to work against 12 of 24 (50%) (p < 0.05) [25]. A 2009 review rated the evidence for chronic pain as fair, from a single study [14].
- Population
- 46 inpatients with chronic pain on multidisciplinary treatment, 22 of whom also had daily far-infrared sauna for 4 weeks [25].
- Sources
- [25], [14]
- Caveats
- The abstract does not say that groups were randomized. Pain scores themselves did not differ between groups.
Fibromyalgia
Limited evidence: pain fell by about half in 13 women with fibromyalgia given Waon therapy, in a study with no control group.
The numbers and sources
- Effect
- All 13 patients reported a reduction in pain of about half after the first session (range 11% to 70%), stable at 20% to 78% after 10 sessions. Pain and Fibromyalgia Impact Questionnaire scores fell significantly (p < 0.01) [26].
- Population
- 13 women with fibromyalgia, mean age 45, treated 2 or 5 days a week [26].
- Sources
- [26]
- Caveats
- No control group and 13 participants, so the change cannot be separated from expectation.
Low back pain
Limited evidence: pain scores fell from a median of 5 to 3 in 37 people after 10 sauna sessions, in a study with no control group.
The numbers and sources
- Effect
- After 10 sessions of 15 minutes at 90°C over 5 days, median pain on a verbal numerical rating scale fell from 5 (range 2 to 8) to 3 (range 0 to 8), and median Oswestry disability scores fell from 12 to 8 (P < 0.001 for both) [21].
- Population
- 37 consecutive patients over 20 years of age with low back pain [21].
- Sources
- [21]
- Caveats
- No control group, so the change cannot be separated from natural recovery or expectation. One week of follow-up.
Fibromyalgia, against aerobic exercise
One trial of 226 adults with fibromyalgia found tai chi improved symptom scores more than aerobic exercise at 24 weeks, by 16.2 points when matched for time.
Compared with supervised aerobic exercise twice a week for 24 weeks [11]
The numbers and sources
- Effect
- Revised Fibromyalgia Impact Questionnaire scores improved 5.5 points more across the combined tai chi groups than with aerobic exercise (95% CI 0.6 to 10.4), and 16.2 points more when tai chi was given at the same dose (95% CI 8.7 to 23.6). Anxiety, self-efficacy and coping also improved more. Twenty-four weeks of tai chi improved scores more than 12 weeks [11].
- Population
- 226 adults with fibromyalgia, 151 in four tai chi groups and 75 in aerobic exercise [11].
- Sources
- [11]
- Caveats
- One single-blind trial. Attendance was higher in tai chi than in aerobic exercise, which may explain part of the difference [11].
Fibromyalgia
Small trials found less pain and better quality of life scores in people with fibromyalgia after a course of sessions, compared with rest or usual care.
The numbers and sources
- Effect
- In 60 patients, pain fell 3.0 points on a visual analogue scale with cryotherapy against 0.3 with rest, and Fibromyalgia Impact Questionnaire scores fell 32.1 against 0.4 (all p < 0.001) [13]. In 24 patients, 10 sessions over 8 days improved health-related quality of life against usual care, lasting at least a month [14].
- Population
- 60 patients in an open crossover trial, with only the first period analyzed [13]. 24 patients, 11 on cryotherapy and 13 controls [14].
- Sources
- [13], [14]
- Caveats
- Open trials with no sham, in a condition where symptoms respond strongly to expectation. A carry-over effect led one trial to discard its second period [13].
Chronic low back pain
Limited evidence: pain and disability scores fell after a course of sessions in two studies with no control group.
The numbers and sources
- Effect
- In 41 adults with chronic low back pain, pain and disability scores fell significantly over 20 sessions in 5 weeks (p < 0.001) [17]. In 30 patients with lumbar spine osteoarthritis who also did therapeutic exercise, back pain fell significantly (p < 0.0001) and plasma cortisol rose (p = 0.0009) [18].
- Population
- 41 adults aged 18 to 65 [17]. 30 patients with lumbar spine osteoarthritis [18].
- Sources
- [17], [18]
- Caveats
- Neither study had a control group, and one combined cryotherapy with exercise [18].
Low back pain
Mixed results: one meta-analysis found pain reduction with higher-dose laser in chronic low back pain, and a later one found the effect against sham clinically unimportant.
The numbers and sources
- Effect
- Across 15 sham-controlled studies (1,039 participants), pain fell by up to 1.40 cm on a 10 cm scale (95% CI -1.91 to -0.88) in trials using at least 3 J per point and in people with pain for under 30 months [15]. Across 12 RCTs (1,046 participants), the effect on pain and disability compared with sham was clinically unimportant in acute, subacute and chronic low back pain, and did not differ meaningfully from exercise [16].
- Population
- Adults with chronic non-specific low back pain [15]. People with acute, subacute or chronic non-specific low back pain [16].
- Sources
- [15], [16]
- Caveats
- The earlier review's benefit appeared only in dose and duration subgroups [15]. The later review concluded current evidence does not support its use for this condition [16].
Period pain, compared with sham TENS
Mixed results: one review of sham-controlled trials found TENS eased period pain in women, while another found pain scores did not differ but fewer women needed pain pills.
Compared with sham TENS [2]; placebo TENS [3]; sham or placebo TENS in most trials, a placebo pill in one and usual NSAID use in one [4]
The numbers and sources
- Effect
- In 4 trials that all used sham TENS, pain was lower with TENS (SMD 1.384, 95% CI 0.505 to 2.262) [2]. In 9 trials against placebo, fewer women needed pain medicine (RR 0.43, 95% CI 0.30 to 0.63, moderate quality) and relief lasted longer, while pooled pain intensity did not differ (SMD -4.50, 95% CI -9.90 to 0.91) [3]. Across 13 trials, mostly against sham, pain scores were lower with TENS (MD -1.97, 95% CI -3.13 to -0.81, 8 trials, 398 women, I² 90%), fewer ibuprofen tablets were taken (MD -1.29, 95% CI -2.54 to -0.05), and scores for pain's effect on daily life did not differ (MD 0.01, 95% CI -0.37 to 0.40) [4].
- Population
- 260 women with primary dysmenorrhea in 4 trials [2]. 530 women in 9 trials [3]. 779 women and girls aged 15 to 29 in 13 trials [4].
- Sources
- [2], [3], [4]
- Caveats
- Trials were small, heterogeneity was very high, and the reviews included different trials [3][4]. TENS produces a tingling that a sham device does not fully copy, so blinding may be imperfect.
Labor pain
Mixed results: a Cochrane review found little difference in labor pain ratings with TENS, while a later review of 26 trials found a small reduction in pain intensity.
Compared with routine care, other pain relief methods or placebo devices [6]; control groups the abstract does not describe [7]
The numbers and sources
- Effect
- Across 19 trials, pain ratings differed little between TENS and control groups. Women given TENS on acupuncture points were less likely to report severe pain (RR 0.41, 95% CI 0.32 to 0.55). Added to an epidural, TENS did not reduce pain, and it had no consistent effect on interventions or outcomes in labor. Most women who used TENS said they would use it again [6]. A later review found a small pooled reduction in pain intensity (RR 1.52, 95% CI 1.35 to 1.70) [7].
- Population
- 1,671 women in labor in 19 trials, 15 with electrodes on the back [6]. 3,348 women in labor in 26 trials [7].
- Sources
- [6], [7]
- Caveats
- Most trials in the later review had a high risk of bias [7]. Use at home in early labor has not been studied [6].
Chronic low back pain
Mixed results: placebo-controlled trials conflicted for chronic low back pain. A 2026 review found an effect only when stimulation was strong enough to feel clearly.
Compared with placebo TENS [10]; control or placebo groups [11]
The numbers and sources
- Effect
- Four high-quality trials gave conflicting results on pain against placebo, and two (410 patients) found no improvement in back function [10]. Across 29 studies, TENS had no overall effect on pain (d 0.16, 64 comparisons). Against control or placebo, trials using a clearly felt, adjusted intensity showed a larger effect (d 0.97, 95% CI 0.65 to 1.30) than trials using too little (d 0.30, 95% CI -0.11 to 0.72) [11].
- Population
- 585 patients in 4 trials [10]. 29 studies [11].
- Sources
- [10], [11]
- Caveats
- The later review rated certainty low because of high risk of bias and heterogeneity [11].
Muscle damage and soreness after exercise
One sham-controlled trial of 32 young men found creatine kinase did not rise after damaging exercise with grounding, while it rose with sham. Pain occurred in both groups.
Compared with sham grounding, with the same equipment not connected to the earth [4][5]
The numbers and sources
- Effect
- After 200 half-knee bends, men grounded for 4 hours on days 1 and 2 had no significant rise in creatine kinase on day 2, while the sham group did (P < 0.01). The between-group difference was significant (P = 0.04). Both groups had pain on every day after exercise [4]. In an 8-person pilot, pain scores and creatine kinase were among the measures that differed by 10% or more between grounded and sham groups [5].
- Population
- 32 healthy young men, 16 grounded and 16 sham [4]. 8 healthy adults, 4 per group [5].
- Sources
- [4], [5]
- Caveats
- The trial was funded by Earth FX Inc., which also supplied the products, and both authors named in its disclosure worked as contractors for Earth FX. The authors state the funder had no role in the study [4]. The pilot set its own 10% threshold rather than testing significance [5].
Endometriosis pain
Limited evidence: one trial of 101 women found pelvic pain eased only when TENS was added to hormonal treatment. A before-and-after study found no significant pain change.
Compared with hormonal treatment alone [14]; the same women before using TENS [15]
The numbers and sources
- Effect
- Pelvic pain fell from 7.11 to 4.55 with TENS added to hormonal treatment (p < 0.001), with relief seen only in that group. Pain during sex improved in both groups [14]. In a study with 3 months without and 3 months with TENS, pain fell 2.29 points (p = 0.44), quality of life improved 16.57 points (p < 0.001) and daily ibuprofen fell 93 mg (p = 0.02) [15].
- Population
- 101 women with deep endometriosis on hormonal treatment, for 8 weeks [14]. Women aged 18 to 45 with surgically confirmed endometriosis [15].
- Sources
- [14], [15]
- Caveats
- The trial abstract reports changes within each group, not a difference between them, and there was no sham [14]. The second study had no control group [15].
Chronic low back pain, against other exercise
Not shown to improve back function or pain more than other back exercise, stretching classes or physical therapy. It was noninferior to physical therapy in one trial.
Compared with back-focused exercise such as physical therapy [1]; conventional stretching classes [2]; 15 physical therapy visits [3]
The numbers and sources
- Effect
- Against back-focused exercise at 3 months, back function differed by 0.38 points (95% CI -1.33 to 0.62, 4 trials, moderate certainty) and pain by 2.68 points on a 0 to 100 scale (95% CI -2.01 to 7.36, very low certainty) [1]. Yoga was not superior to conventional stretching exercises at any time point [2]. Yoga met the noninferiority margins against physical therapy for function and pain at 12 weeks, and both were maintained at 1 year [3].
- Population
- 912 participants in 8 trials [1]. 183 adults in the yoga and stretching arms [2]. 320 adults [3].
- Sources
- [1], [2], [3]
- Caveats
- Participants were not blinded, and the physical therapy group had more loss to follow-up [3].
Knee osteoarthritis, against physical therapy
One trial of 204 adults found tai chi and physical therapy eased knee osteoarthritis symptoms by similar amounts at 12 weeks, maintained to 52 weeks.
Compared with standard physical therapy twice a week for 6 weeks, then 6 weeks of monitored home exercise [10]
The numbers and sources
- Effect
- WOMAC scores fell 167 points with tai chi and 143 points with physical therapy at 12 weeks, a difference of 24 points (95% CI -10 to 58) that was not significant. Tai chi produced greater improvement in depression and in the physical component of quality of life [10].
- Population
- 204 adults with symptomatic knee osteoarthritis, mean age 60, 70% women [10].
- Sources
- [10]
- Caveats
- Patients knew their group. One urban academic hospital [10].
Period pain, compared with pain medicines and other treatments
Limited evidence: in single small trials, period pain did not differ between TENS and acetaminophen in women. Too few trials compared TENS with NSAIDs for pain.
Compared with acetaminophen [5]; acupressure [5]; interferential current therapy [5]
The numbers and sources
- Effect
- Pain did not differ between high-frequency TENS and acetaminophen (MD -0.98, 95% CI -3.30 to 1.34, 1 trial, 20 women) or low-frequency TENS and acetaminophen (MD -1.48, 95% CI -3.61 to 0.65). Nor did it differ against acupressure (MD -0.66, 18 women) or interferential current (MD -0.03, 95% CI -1.04 to 0.98, 2 trials, 62 women) [5].
- Population
- 18 to 62 women per comparison [5].
- Sources
- [5]
- Caveats
- Very low certainty, from one or two trials per comparison [5].
Endometriosis pain
Not studied in people. Users report: 70% of 484 Australian women with endometriosis used heat, rating it 6.5 out of 10 for pain relief.
No study in people. This rests on what users report.
The numbers and sources
- Effect
- In a national online survey, heat was the most common self-management strategy (70%), with a mean self-rated effectiveness for pain of 6.52 on a 10-point scale [12]. A narrative review notes that women with endometriosis frequently use heating devices for period and pelvic pain [13].
- Population
- 484 women aged 18 to 45 in Australia with confirmed endometriosis, recruited through support groups [12].
- Sources
- [12], [13]
- Caveats
- A self-selected survey with no comparison group. No trial of heat for endometriosis pain was located.
Daily life
Period pain in trials
Shown in two reviews of trials to lower period pain in women with primary dysmenorrhea, by about 2 to 2.5 cm on a 10 cm pain scale.
Compared with no treatment [23]; mefenamic acid in one trial [23]; comparators of any kind, not described in the source abstract [24]
The numbers and sources
- Effect
- Against no exercise, exercise lowered period pain (SMD -1.86, 95% CI -2.06 to -1.66, 9 RCTs, 632 women, low-quality evidence), about 25 mm on a 100 mm scale. Whether adverse events differed was uncertain [23]. A second review found pain intensity 1.89 cm lower on a visual analogue scale (95% CI 1.09 to 2.96) and pain lasting 3.92 hours less (95% CI 2.97 to 4.86), with moderate-quality evidence for intensity [24].
- Population
- 854 women with moderate to severe primary dysmenorrhea in 12 trials, 754 pooled [23]; 1,681 women in 15 RCTs, 11 pooled [24].
- Sources
- [23], [24]
- Caveats
- Heterogeneity was high in both reviews, and no trial compared exercise with an attention control [23][24]. Trials used stretching, core work, yoga, Zumba or aerobic training, about 45 to 60 minutes three or more times a week [23].
Endometriosis symptoms in trials
Limited evidence: a review of 6 small trials found exercise improved pain-related quality of life in women with endometriosis, from a pooled analysis of 2 trials.
Compared with activities of daily living or conventional treatment [26]
The numbers and sources
- Effect
- The trials reported better quality of life, pain intensity, mental health, pelvic floor function and bone density with exercise. Pooling 2 trials, the pain domain of quality of life improved (P < 0.0001), along with control and powerlessness and emotional well-being [26].
- Population
- 251 women with endometriosis in 6 RCTs [26].
- Sources
- [26]
- Caveats
- Outcomes differed between trials and were incompletely reported, so only 2 could be pooled. Trials were short, and the abstract gives no effect size for pain [26].
Neck and shoulder pain
One trial in office workers found less neck and shoulder pain after 3 months of a program to cut sitting, and no change in back pain.
Compared with control offices whose workers behaved as usual [12]
The numbers and sources
- Effect
- At 3 months, the odds of neck and shoulder pain were lower in the program group (OR 0.52, 95% CI 0.30 to 0.92), with no difference at 1 month. Back and limb pain did not differ. Total pain score fell slightly [12].
- Population
- 317 office workers in 19 offices [12].
- Sources
- [12]
- Caveats
- Pain was a secondary outcome, self-reported by workers who knew their group.