6.9Pain

RCTs and CCTs
Review detailsInterventionPopulationResultsQuality assessment+
Author (year)
Campbell (2001)[404]

Objective
To establish whether cannabis is an effective and safe treatment option in the management of pain.

Number of included studies
7 RCTs and 2 "n of 1 within patient cross-over trials"
Cannabinoids versus oral codeine, oral secobarbital and placebo.Patients with different types of pain: cancer (n=5) ; acute post-operative pain (n=2); chronic non-malignant pain (n=2)Acute post-operative pain: in the 2 trials levonantradol was superior to placebo but no more effective than codeine.

Cancer: 4/5 of the trials found the cannabinoid as effective as codeine, but with dose limiting adverse effects.
Benzopyranoperidine tested in the remaining trial was ineffective compared with both codeine and placebo.

Post-operative pain: In both trials Levonantradol was more effective than placebo when administered intramuscularly. However, adverse effects with Levonantradol were common, although considered mild.

Non-malignant pain: In only 1 of the 2 "no of 1" studies was oral delta-9-tetrahydrocannabinol found to be significantly more effective than placebo.

Adverse effects: Adverse effects associated with the cannabinoids were common and sometimes severe in 6/8 trials that showed efficacy. The predominant adverse effect was depression of the central nervous system.
1: Good
2: Good
3: Good
4: Good
5: Good
Author (year)
Carroll (2002)[398]

Objective
To evaluate the effectiveness of TENS in chronic pain

Number of included studies
19 RCTs
TENS (19 RCTs)Patients with chronic pain for 3 months or more. Patients with headache, migraine and dysmenorrhoea were excluded.In 10 of 15 inactive control studies there was a positive analgesic effect in favour of active TENS treatment. For the multiple dose treatment comparison studies only 3/7 were considered to be in favour of the active TENS treatments. For the active controlled studies, 7 studies made direct comparisons between HRTENS and LFTENS. 5/7 studies found no difference in terms of analgesic efficacy between the two treatments.

The published trials do not provide information on the stimulation parameters which are most likely to provide optimum pain relief, nor do they answer questions about long-term effectiveness.
1: Good
2: Good
3: Good
4: Good
5: Good
Author (year)
Ernst (2000)[399]

Objective
To assess whether phytodolor is effective in treating musculoskeletal pain.

Number of included studies
10 double blind RCTs (3 included 3 treatment arms)
Phytodolor vs placebo (n=6)
Phytodolor vs active medication (n=7)
Patients with osteoarthritis, chronic epicondylitis, and various rheumatic diseasesPhytodolor was more effective than placebo and as effective as synthetic drugs in the symptomatic treatment of musculoskeletal pain.1: Good
2: Good
3: Good
4: Good
5: Good
Author (year)
Ezzo (2000)[400]

Objective
To assess the effectiveness of acupuncture as a treatment for chronic pain

Number of included studies
51 RCTs
Acupuncture with needles versus sham acupuncture, placebo or usual care.Patients with chronic pain conditions: angina, osteoarthritis, Raynauds, post herpes, pancreatitis, fibromyalgia, musculoskeletal, dysmennorrhea, myalgia, headache, migraine and lower back pain.Results were positive in 21 studies, negative in 3 and neutral in 27. 6 or more acupuncture treatments were significantly associated with positive outcomes. Overall, the results give limited evidence that acupuncture is more effective than no treatment for chronic pain and inconclusive evidence that acupuncture is more effective than placebo, sham acupuncture or standard care.1: Good
2: Good
3: Good
4: Fair
5: Good
Author (year)
Fernandez (1989)[388]

Objective
To assess the efficacy of cognitive coping strategies for altering the perception of pain.

Number of included studies
60 CCTs
External focus of attention (n=14); neutral imaginings (n=7); pleasant imaginings (n=20); rhythmic cognitive activity v (n= 5); pain acknowledging (n=15): all vs no treatment. Cognitive strategies vs expectancy control. (n=13)Not stated.85% of the time, cognitive strategies had a positive effect in enhancing pain tolerance/threshold or attenuating pain ratings as compared to no treatment. Imagery methods were the most effective and pain acknowledging the least effective method. Positive expectancy is no better than no treatment.1: Fair
2: NA
3: NA
4: Fair
5: Fair
Author (year)
Fishbain (2000)[393]

Objective
To investigate whether antidepressants have an analgesic effect for chronic pain independent of their antidepressant effect

Number of included studies
30 RCTs and 4SRs
Antidepressants (S-Adenosylmethionine, amitriptyline, desipramine, trazadone, clomipramine, imipramine, trimipramine, mianserine, fluoxetine, citalopram, cyclobenzaprine)Patients with osteoarthritis, rheumatoid arthritis, fibrositis, fibromyalgia, facial pain, chronic pain, neuropathic pain, and psychogenic pain.Antidepressants were not consistently effective for osteoarthritic or rheumatoid pain, but the serotonergic-non-adrenergic agents were more consistently effective than the serotonergic agents. Serotenergic-noradrenergic antidepressants were consistently effective for fibrositis or fibromyalgia pain whereas serotenergic agents were not. Two trials reported a positive effect for the treatment of facial pain. All four SRs reported that antidepressants do have an analgesic effect. However, these reviews pooled data from different types of antidepressants and so give no indication of what types of antidepressant are most effective.

Overall antidepressants may have an analgesic effect in chronic pain, and these drugs were effective for neuropathic pain.
1: Fair
2: Good
3: NA
4: Fair
5: Good
Author (year)
Furlan (2001)[397]

Objective
To determine if chemical sympathectomy successfully reduces limb neuropathic pain

Number of included studies
13 studies (n=66): 2 RCTs, 1 CCT, 5 case series, and 5 case reports.
Lumbar chemical sympathectomy and cervico-thoracic chemical sympathectomy performed with phenol or alcohol.Patients with CRPS and postherpetic neuralgiaMeaningful pain relief was reported in 28/63 patients with CRPS and in all patients with postherpetic neuralgia. Reported complications were mild post-sympathectomy neuralgia (n=5), sever post-sympathectomy neuralgia (n=3), iliac fossa pain, alteration of menstrual periods (n=1) and episodes of diarrhoea (n=1). The evidence provided by the studies was not convincing regarding the effectiveness of chemical sympathectomy for neuropathic pain given the small number of patients, short follow-up and the poor description of outcomes. The results of the RCTs were not reported separately or in tables, thus the results of these could not be considered separately.1: Good
2: Good
3: NA
4: Fair
5: Poor
Author (year)
Gam (1995)[402]

Objective
To assess the efficacy of ultrasound in the treatment of pain in musculoskeletal disorders.

Number of included studies
22 CCTs
Ultrasound versus placebo ultrasound, TENS and placebo ultrasound, TENS, TENS and steroid injection, Short-wave, ICE.Patients with a variety of musculoskeletal diseases: lateral epicondylitis, osteoarthritis, bursitis of the shoulder, traumatized perineum, ankle distortion, lower back pain, myofacial pain.Overall no significant reduction in pain was observed in the treatment group relative to the control group in either trials including a 'sham' ultra-sound treatment as the control or those including a non ultra-sound treatment or no treatment as the control.1: Good
2: Fair
3: Poor
4: Poor
5: Fair
Author (year)
Gam (1993)[403]

Objective
To undertake a meta-analysis of the published effect of low-level laser therapy (LLLT) on musculoskeletal pain

Number of included studies
17 RCTs (10 double blind) and 6 uncontrolled studies.
LLLT compared to placeboPatients with osteoarthritis, craniomandibular disorders, ankle sprains, rheumatoid arthritis, tendonitis, cervical and lumbar syndromes, epicondylitis lateralis, chronic oro-facial pain, chronic low back pain, trigger points, and chronic myofacial painNine double blind and 4 unblind RCTs presented results in a form which allowed pooling. The results indicate that LLLT had no effect on pain in musculoskeletal syndromes.1: Fair
2: Fair
3: Fair
4: Poor
5: Fair
Author (year)
Karjalainen (2002)[390]

Objective
To determine the effectiveness of multidisciplinary rehabilitation for widespread musculoskeletal pain among working age adults.

Number of included studies
7 RCTs (n=1050)
Education plus physical training/cognitive treatment vs education vs waiting list controls; behavioural therapy vs education; stress management vs aerobic exercise vs normal treatment (4 poor quality RCTs)
Outpatient multidisciplinary rehabilitation; behavioural therapy vs waiting list controls (3 RCTs)
Patients with fibromyalgia and widespread musculoskeletal painThe RCTs on fibromyalgia suggested no quantifiable benefits. The RCTs on musculoskeletal pain found no evidence of efficacy. However, behavioural treatment and stress management appear to be important components. Education combined with physical training showed some positive effects in long term follow-up.1: Good
2: Good
3: Good
4: Good
5: Good
Author (year)
McQuay (1996)[392]

Objective
To assess the effectiveness and safety of antidepressants in neuropathic pain.

Number of included studies
17 RCTs ( n= 773 participants)
Antidepressants including: nortriptyline; fluphenazine; imipramine; amitriptyline; desipramine; fluoxetine; clomipramine; paroxetine; citalopram; mianserin.Patients with neuropathic pain: diabetic neuropathy, postherpetic neuralgia, atypical facial pain and central pain.6/13 diabetic neuropathy studies showed significant benefit compared to placebo with 9 different antidepressants. Imipramine, desipramine and the combined tricyclics were the most effective interventions. Paroxetine and fluoxetine were less effective and mianserin was no different from placebo.

2/3 studies in postherpetic neuralgia showed a significant benefit compared to placebo, and both the atypical facial pain studies showed benefit.
Comparisons of tricyclic antidepressants did not show any significant difference between them; they were significantly more effective than benzodiazepines. paroxetine and mianserin were less effective than Imipramine.
1: Good
2: Good
3: Good
4: Good
5: Good
Author (year)
McQuay (1995)[395]

Objective
To determine the effectiveness and adverse effects of anticonvulsant drugs in the management of pain.

Number of included studies
20 RCTs
Carbamazepine (n=10); Phenytoin (n=5); Clonazepam (n=3); Sodium Valproate (n=2).Patients with chronic non-malignant pain, cancer pain, postoperative pain and acute herpes zosterThe only placebo controlled study in acute pain found no analgesic effect of sodium valproate. For treating trigeminal neuralgia, carbamazepine was shown to have a significant beneficial effect relative to placebo. For diabetic neuropathy, both carbamazepine and phenytoin were shown to be effective in reducing pain levels. In migraine prophylaxis 2/3 of the studies (using carbamazepine and sodium valproate) showed significant benefits relative to placebo. There was no differential effect seen with clonzazepin within this patient group.

Other pain syndromes: Phenytoin had no effect on the irritable bowel syndrome and carbamazepine had little effect on pain after stroke. However, clonazepam was effective in one study for temporomandibular joint dysfunction.

Overall: Anticonvulsants were shown to be effective for trigeminal neuralgia, diabetic neuropathy and for migraine prophylaxis. However, minor adverse effects occurred as often as benefit.
1: Good
2: Fair
3: Good
4: Good
5: Good
Author (year)
Mellegers (2001)[396]

Objective
To assess the efficacy/effectiveness and side effects of gabapentin for the treatment of neuropathic pain

Number of included studies
31 studies: 6 RCTs, 25 uncontrolled studies: 2 open label trials, 1 retrospective review of charts, 7 case reports, and 15 case series
Gabapentin 100–3600mg/day compared to placebo (n=4) or amitriptyline (n=2) or uncontrolled (n=25).Patients with central pain, CRPS, mixed nociceptive and neuropathic pain, diabetic neuropathy, postherpetic neuralgia, trigeminal neuralgia, mixed neuropathic painThe meta-analysis of 4 placebo controlled trials showed a positive effect of gabapentin in diabetic neuropathy and post-herpetic neuralgia. The uncontrolled studies demonstrated positive effects on pain in different neuropathic syndromes, as well as benefit on different types of neuropathic pain. Intolerable side effects were reported in 10.5% of patients who received gabapentin in the RCTs and 4.4% of patients in the uncontrolled studies. The most common reported side effects included dizziness, somnolence, GI complaints, sedation, ataxia, oedema, and headache. Gabapentin seems to be effective in multiple painful neuropathic conditions.1: Good
2: Good
3: Good
4: Good
5: Good
Author (year)
Morley (1999)[389]

Objective
To assess the efficacy of cognitive-behavioural therapy (including behaviour therapy) for chronic pain in adults, excluding headache.

Number of included studies
25 RCTs
Cognitive behavioural therapy and behavioural therapy versus pain coping skills training; in and out-patient pain management; applied relaxation and biofeedback; waiting list controls.In and out patients with lower back pain, rheumatoid arthritis, chronic musculoskeletal pain, and osteoarthritis (knee).When compared to the waiting list control groups cognitive-behavioural treatments were associated with significantly greater changes across all domains of measurement. Comparison with alternative active treatments revealed that cognitive-behavioural treatments produced significantly greater changes for the domains of pain experience, cognitive coping and appraisal (positive coping measure), and reduced behavioural expression of pain. Differences on the following domains were not significant; mood/affect (depression and other, non-depression, measures), cognitive coping and appraisal (negative, catastrophization) and social role functioning. Overall, active psychological treatments based on the principal of CBT are effective for chronic pain management.1: Good
2: Good
3: Fair
4: Good
5: Good
Author (year)
Sindhu (1996)[391]

Objective
To assess the effectiveness of non-pharmacological interventions on the management of pain.

Number of included studies
49 RCTs
Multidisciplinary approach to assisting patients; biofeedback and relaxation; relaxation; tape recordings; 30 mins information re coping strategies; nursing interaction in the form of cards; pre-operative information; education interventionNot reportedAlthough there is evidence in the form of primary studies to suggest that non-pharmacological nursing interventions are effective in the management of pain the studies were too heterogeneous to detect a difference between the treatment and control groups.1: Good
2: Fair
3: NA
4: Fair
5: Poor
Author (year)
van der Windt (1999)[401]

Objective
To evaluate the effectiveness of ultrasound therapy in the treatment of musculoskeletal disorders.

Number of included studies
38 RCTs
Ultrasound therapyPatients with lateral epicondylitis, shoulder pain, degenerative rheumatic disorders, ankle distortions, temporomandibular pain, myofacial pain and other musculoskeletal disorders.11/13 placebo controlled trials of reasonable methodological quality found no evidence of clinically important or statistically significant results. There seems to be little evidence to support the use of ultrasound therapy in the treatment of musculoskeletal disorders.1: Good
2: Good
3: Good
4: Good
5: Good
Author (year)
Wiffen (2001)[394]

Objective
To evaluate the analgesic effectiveness and adverse effects of anticonvulsant drugs for pain management in clinical practice.

Number of included studies
23 RCTs (n=1074)
Carbamazepine (n=12)
Gabapentin (n=2)
Phenytonin (n=6)
Clonazepam (n=1)
Sodium valporate (n=2)
Patients with trigeminal neuralgia, post-stroke pain, diabetic neuropathy, acute herpes zoster, cancer pain, post-herpetic neuralgia, irritable bowel syndrome, rheumatoid arthritis, temporomandibular joint dysfunction, acute post-op pain and spinal cord injury.Few trials showed analgesic effectiveness. No trials compared different anticonvulsants. There is no evidence that anticonvulsants are effective for acute pain. In chronic pain syndromes other than trigeminal neuralgia, anticonvulsants should be with held until other interventions have been tried. While gabapentin is increasingly used for neuropathic pain the evidence would suggest that it is not superior to carbamazepine.1: Good
2: Good
3: Good
4: Good
5: Fair

From: Appendix I, Evidence tables

Cover of Multiple Sclerosis
Multiple Sclerosis: National Clinical Guideline for Diagnosis and Management in Primary and Secondary Care.
NICE Clinical Guidelines, No. 8.
National Collaborating Centre for Chronic Conditions (UK).
Copyright © 2004, Royal College of Physicians of London.

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