An observational descriptive study of the epidemiology and treatment of neuropathic pain in a UK general population.

BACKGROUND: This study updated our knowledge of UK primary care neuropathic pain incidence rates and prescribing practices. METHODS: Patients with a first diagnosis of post-herpetic neuralgia (PHN), painful diabetic neuropathy (PDN) or phantom limb pain (PLP) were identified from the General Practice Research Database (2006 - 2010) and incidence rates were calculated. Prescription records were searched for pain treatments from diagnosis of these conditions and the duration and daily dose estimated for first-line and subsequent treatment regimens. Recording of neuropathic back and post-operative pain was investigated. RESULTS: The study included 5,920 patients with PHN, 5,340 with PDN, and 185 with PLP. The incidence per 10,000 person-years was 3.4 (95% CI 3.4, 3.5) for PHN; and 0.11 (95% CI 0.09, 0.12) for PLP. Validation of the PDN case definition suggested that was not sensitive. Incident PHN increased over the study period. The most common first-line treatments were amitriptyline or gabapentin in the PDN and PLP cohorts, and amitriptyline or co-codamol (codeine-paracetamol) in PHN. Paracetamol, co-dydramol (paracetamol-dihydrocodeine) and capsaicin were also often prescribed in one or more condition. Most first-line treatments comprised only one therapeutic class. Use of antiepileptics licensed for neuropathic pain treatment had increased since 2002-2005. Amitriptyline was the only antidepressant prescribed commonly as a first-line treatment. CONCLUSION: The UK incidence of diagnosed PHN has increased with the incidence of back-pain and post-operative pain unclear. While use of licensed antiepileptics increased, prescribing of therapy with little evidence of efficacy in neuropathic pain is still common and consequently treatment was often not in-line with current guidance.

Single dose oral analgesics for acute postoperative pain in adults.

BACKGROUND: Thirty-five Cochrane Reviews of randomised trials testing the analgesic efficacy of individual drug interventions in acute postoperative pain have been published. This overview brings together the results of all those reviews and assesses the reliability of available data. OBJECTIVES: To summarise data from all Cochrane Reviews that have assessed the effects of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery, who have been given a single dose of oral analgesic taken alone. METHODS: We identified systematic reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single Review Group, had a standard title, and had as their primary outcome numbers of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews we extracted the number needed to treat (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, the percentage of participants remedicating by 6, 8, 12, or 24 hours, and results for participants experiencing at least one adverse event. MAIN RESULTS: The overview included 35 separate Cochrane Reviews with 38 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 45,000 participants studied in approximately 350 individual studies. The individual reviews included only high-quality trials of standardised design and outcome reporting. The reviews used standardised methods and reporting for both efficacy and harm. Event rates with placebo were consistent in larger data sets. No statistical comparison was undertaken.There were reviews but no trial data were available for acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for dexibuprofen, dextropropoxyphene 130 mg, diflunisal 125 mg, etoricoxib 60 mg, fenbufen, and indometacin. Where there was adequate information for drug/dose combinations (at least 200 participants, in at least two studies), we defined the addition of four comparisons of typical size (400 participants in total) with zero effect as making the result potentially subject to publication bias and therefore unreliable. Reliable results were obtained for 46 drug/dose combinations in all painful postsurgical conditions; 45 in dental pain and 14 in other painful conditions.NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief over four to six hours compared with placebo. The proportion of participants achieving this level of benefit varied from about 30% to over 70%, and the time to remedication varied from two hours (placebo) to over 20 hours in the same pain condition. Participants reporting at least one adverse event were few and generally no different between active drug and placebo, with a few exceptions, principally for aspirin and opioids.Drug/dose combinations with good (low) NNTs were ibuprofen 400 mg (2.5; 95% confidence interval (CI) 2.4 to 2.6), diclofenac 50 mg (2.7; 95% CI 2.4 to 3.0), etoricoxib 120 mg (1.9; 95% CI 1.7 to 2.1), codeine 60 mg + paracetamol 1000 mg (2.2; 95% CI 1.8 to 2.9), celecoxib 400 mg (2.5; 95% CI 2.2 to 2.9), and naproxen 500/550 mg (2.7; 95% CI 2.3 to 3.3). Long duration of action (≥ 8 hours) was found for etoricoxib 120 mg, diflunisal 500 mg, oxycodone 10 mg + paracetamol 650 mg, naproxen 500/550 mg, and celecoxib 400 mg.Not all participants had good pain relief and for many drug/dose combinations 50% or more did not achieve at last 50% maximum pain relief over four to six hours. AUTHORS' CONCLUSIONS: There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. There is also important information on drugs for which there are no data, inadequate data, or where results are unreliable due to susceptibility to publication bias. This should inform choices by professionals and consumers.

Interference with work in fibromyalgia: effect of treatment with pregabalin and relation to pain response.

BACKGROUND: Clinical trials in chronic pain often collect information about interference with work as answers to component questions of commonly used questionnaires but these data are not normally analysed separately. METHODS: We performed a meta-analysis of individual patient data from four large trials of pregabalin for fibromyalgia lasting 8-14 weeks. We analysed data on interference with work, inferred from answers to component questions of Fibromyalgia Impact Questionnaire (FIQ), Short Form 36 Health Survey, Sheehan Disability Scale, and Multidimensional Assessment of Fatigue, including "How many days in the past week did you miss work, including housework, because of fibromyalgia?" from FIQ. Analyses were performed according to randomised treatment group (pregabalin 150-600 mg daily or placebo), pain improvement (0-10 numerical pain rating scale scores at trial beginning vs. end), and end of trial pain state (100 mm visual analogue pain scale [VAS]). RESULTS: Comparing treatment group average outcomes revealed modest improvement over the duration of the trials, more so with active treatment than with placebo. For the 'work missed' question from FIQ the change for patients on placebo was from 2.2 (standard deviation [SD] 2.3) days of work lost per week at trial beginning to 1.9 (SD 2.1) days lost at trial end (p < 0.01). For patients on 600 mg pregabalin the change was from 2.1 (SD 2.2) days to 1.6 (SD 2.0) days (p < 0.001). However, the change in days of work lost was substantial in patients with a good pain response: from 2.0 (SD 2.2) days to 0.97 (SD 1.6) days (p < 0.0001) for those experiencing >/= 50% pain improvement and from 1.9 (SD 2.2) days to 0.73 (SD 1.4) days (p < 0.0001) for those achieving a low level of pain at trial end (<30 mm on the VAS). Patients achieving both >/= 50% pain improvement and a pain score <30 mm on the VAS had the largest improvement, from 2.0 (SD 2.2) days to 0.60 (SD 1.3) days (p < 0.0001). Analysing answers to the other questions yielded qualitatively similar results. CONCLUSIONS: Effective pain treatment goes along with benefit regarding work. A reduction in time off work >1 day per week can be achieved in patients with good pain responses.

WITHDRAWN: Gabapentin for acute and chronic pain.

BACKGROUND: February 2009: The authors are aware of unpublished trial data for Gabapentin which could affect the results of this review. This information together with that from trials published since 2005, will be considered when this review is updated in 2009.Anticonvulsant drugs have been used in the management of pain since the 1960s. The clinical impression is that they are useful for chronic neuropathic pain, especially when the pain is lancinating or burning. OBJECTIVES: To evaluate the analgesic effectiveness and adverse effects of gabapentin for pain management in clinical practice. SEARCH STRATEGY: Randomised trials of gabapentin in acute, chronic or cancer pain were identified by MEDLINE (1966 to Nov 2004), EMBASE (1994 to Nov 2004), SIGLE (1980 to Jan 2004) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 4, 2004). Additional studies were identified from the reference list of the retrieved papers, and by contacting investigators. Date of most recent search: January 2004. SELECTION CRITERIA: Randomised trials reporting the analgesic effects of gabapentin in participants with subjective pain assessment as either the primary or a secondary outcome. DATA COLLECTION AND ANALYSIS: Data were extracted by two independent review authors, and trials were quality scored. Numbers-needed-to-treat-to-benefit (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse effects and drug-related study withdrawal. MAIN RESULTS: Fourteen reports describing 15 studies of gabapentin were considered eligible (1468 participants). One was a study of acute pain. The remainder included the following conditions: post-herpetic neuralgia (two studies), diabetic neuropathy (seven studies), a cancer related neuropathic pain (one study) phantom limb pain (one study), Guillain Barré syndrome (one study), spinal chord injury pain (one study) and various neuropathic pains (one study).The study in acute post-operative pain (70 participants) showed no benefit for gabapentin compared to placebo for pain at rest.In chronic pain, the NNT for improvement in all trials with evaluable data is 4.3 (95% CI 3.5 to 5.7). Forty two percent of participants improved on gabapentin compared to 19% on placebo. The number needed to harm (NNH) for adverse events leading to withdrawal from a trial was not significant. Fourteen percent of participants withdrew from active arms compared to 10% in placebo arms. The NNH for minor harm was 3.7 (95% CI 2.4 to 5.4). The NNT for effective pain relief in diabetic neuropathy was 2.9 (95% CI 2.2 to 4.3) and for post herpetic neuralgia 3.9 (95% CI 3 to 5.7). AUTHORS' CONCLUSIONS: There is evidence to show that gabapentin is effective in neuropathic pain. There is limited evidence to show that gabapentin is ineffective in acute pain.

Single dose oral mefenamic acid for acute postoperative pain in adults.

BACKGROUND: Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID). It is most often used for treating pain of dysmenorrhoea in the short term (seven days or less), as well as mild to moderate pain including headache, dental pain, postoperative and postpartum pain. It is widely available in many countries worldwide. OBJECTIVES: To assess the efficacy of single dose oral mefenamic acid in acute postoperative pain, and any associated adverse events. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to December 2010. SELECTION CRITERIA: Single oral dose, randomised, double-blind, placebo-controlled trials of mefenamic acid for relief of established moderate to severe postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Studies were assessed for methodological quality and the data extracted by two review authors independently. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours was used to calculate the number of participants achieving at least 50% pain relief. These derived results were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. MAIN RESULTS: Four studies with 842 participants met the inclusion criteria; 126 participants were treated with mefenamic acid 500 mg, 67 with mefenamic acid 250 mg, 197 with placebo, and 452 with lignocaine, aspirin, zomepirac or nimesulide. Participants had pain following third molar extraction, episiotomy and orthopaedic surgery. The NNT for at least 50% pain relief over 6 hours with a single dose of mefenamic acid 500 mg compared to placebo was 4.0 (2.7 to 7.1), and the NNT to prevent use of rescue medication over 6 hours was 6.5 (3.6 to 29). There were insufficient data to analyse other doses or active comparators, or numbers of participants experiencing any adverse events. No serious adverse events or adverse event withdrawals were reported in these studies. AUTHORS' CONCLUSIONS: Oral mefenamic acid 500 mg was effective at treating moderate to severe acute postoperative pain, based on limited data. Efficacy of other doses, and safety and tolerability could not be assessed.

Gabapentin for chronic neuropathic pain and fibromyalgia in adults.

BACKGROUND: This review updates parts of two earlier Cochrane reviews investigating effects of gabapentin in chronic neuropathic pain (pain due to nerve damage). Antiepileptic drugs are used to manage pain, predominantly for chronic neuropathic pain, especially when the pain is lancinating or burning. OBJECTIVES: To evaluate the analgesic effectiveness and adverse effects of gabapentin for chronic neuropathic pain management. SEARCH STRATEGY: We identified randomised trials of gabapentin in acute, chronic or cancer pain from MEDLINE, EMBASE, and CENTRAL. We obtained clinical trial reports and synopses of published and unpublished studies from Internet sources. The date of the most recent search was January 2011. SELECTION CRITERIA: Randomised, double-blind studies reporting the analgesic and adverse effects of gabapentin in neuropathic pain with assessment of pain intensity and/or pain relief, using validated scales. Participants were adults aged 18 and over. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. We calculated numbers needed to treat to benefit (NNTs), concentrating on IMMPACT (Initiative on Methods, Measurement and Pain Assessment in Clinical Trials) definitions of at least moderate and substantial benefit, and to harm (NNH) for adverse effects and withdrawal. Meta-analysis was undertaken using a fixed-effect model. MAIN RESULTS: Twenty-nine studies (3571 participants), studied gabapentin at daily doses of 1200 mg or more in 12 chronic pain conditions; 78% of participants were in studies of postherpetic neuralgia, painful diabetic neuropathy or mixed neuropathic pain. Using the IMMPACT definition of at least moderate benefit, gabapentin was superior to placebo in 14 studies with 2831 participants, 43% improving with gabapentin and 26% with placebo; the NNT was 5.8 (4.8 to 7.2). Using the IMMPACT definition of substantial benefit, gabapentin was superior to placebo in 13 studies with 2627 participants, 31% improving with gabapentin and 17% with placebo; the NNT was 6.8 (5.6 to 8.7). These estimates of efficacy are more conservative than those reported in a previous review. Data from few studies and participants were available for other painful conditions.Adverse events occurred significantly more often with gabapentin. Persons taking gabapentin can expect to have at least one adverse event (66%), withdraw because of an adverse event (12%), suffer dizziness (21%), somnolence (16%), peripheral oedema (8%), and gait disturbance (9%). Serious adverse events (4%) were no more common than with placebo.There were insufficient data for comparisons with other active treatments. AUTHORS' CONCLUSIONS: Gabapentin provides pain relief of a high level in about a third of people who take if for painful neuropathic pain. Adverse events are frequent, but mostly tolerable. More conservative estimates of efficacy resulted from using better definitions of efficacy outcome at higher, clinically important, levels, combined with a considerable increase in the numbers of studies and participants available for analysis.

Minimum efficacy criteria for comparisons between treatments using individual patient meta-analysis of acute pain trials: examples of etoricoxib, paracetamol, ibuprofen, and ibuprofen/paracetamol combinations after third molar extraction.

We defined response in acute pain trials according to percentage of maximum possible efficacy. Minimum efficacy criteria (MEC) of 0%, or at least 15%, 30%, 50%, and 70% pain relief were used to examine stability over time using total pain relief and summed pain intensity difference (SPID), sex differences, and sensitivity. We used individual patient data from placebo-controlled third molar extraction trials: 4 with single-dose oral etoricoxib 120 mg, and 2 with paracetamol, ibuprofen, and ibuprofen plus paracetamol combinations. With etoricoxib, numbers needed to treat (NNTs) were stable between response levels of at least 15% (MEC15) and 50% pain relief (MEC50), and similar for total pain relief and SPID. NNTs were higher (worse) at extremes of MEC, especially with SPID. Results for women and men were similar. NNTs of lower efficacy treatments (paracetamol 500 and 1000 mg) rose rapidly at higher MEC. NNTs of high efficacy treatments (ibuprofen plus paracetamol combinations) showed greater separation at higher MEC. The highest degree of discrimination between treatments was with MEC50 and MEC70. Etoricoxib 120 mg (NNT for ≥50% maximum 6-hour pain relief 1.7) and ibuprofen 200/400 mg plus paracetamol 500/1000 mg (NNTs 1.5 and 1.6, respectively) produced the lowest (best) NNTs in the dental pain model. Timing of patient request for additional analgesia is an alternative analgesic efficacy outcome measure.

Mean analgesic consumption is inappropriate for testing analgesic efficacy in post-operative pain: analysis and alternative suggestion.

BACKGROUND AND OBJECTIVE: Post-operative analgesic consumption is often used as a surrogate measure for pain; analyses of mean data assume a Gaussian distribution and use parametric statistics to assess statistical differences, often in small samples. We used a large individual patient dataset to examine the distribution of analgesic consumption, the validity of such analyses and alternative dichotomous outcomes. METHODS: Analysis of individual patient data from 913 patients over 48 post-operative hours in five randomised trials. Patients had either epidural injection of placebo or morphine (as sulphate and extended release epidural morphine) and use of patient-controlled analgesia. Post-operative fentanyl consumption was calculated over 0-24, 24-48 and 0-48 h. RESULTS: The distribution of analgesic consumption for all patients over the periods 0-24, 24-48 and 0-48 h was exponential. Most patients used less than 750 µg fentanyl over 48 h; 34% used over 1000 µg fentanyl (100 mg morphine), 13% over 2000 µg and 5% over 3000 µg. Mean, median and mode were very different; 20% of patients consumed almost 60% of post-operative analgesic, and standard deviations were generally larger than means. A useful dichotomous outcome was less than 750 µg fentanyl consumed over 48 h, a level associated with very good or excellent patient pain rating. Use of very good or excellent patient pain rating differentiated between different doses of epidural morphine. CONCLUSION: Because of a highly skewed distribution, post-operative analgesic consumption is an uncertain method of measuring analgesic efficacy of an intervention designed to limit pain during and after surgery.

Carbamazepine for acute and chronic pain in adults.

BACKGROUND: Carbamazepine is used to treat chronic neuropathic pain. OBJECTIVES: Evaluation of analgesic efficacy and adverse effects of carbamazepine for acute and chronic pain management (except headaches). SEARCH STRATEGY: Randomised controlled trials (RCTs) of carbamazepine in acute, chronic or cancer pain were identified, searching MEDLINE, EMBASE, SIGLE and Cochrane CENTRAL to June 2010, reference lists of retrieved papers, and reviews. SELECTION CRITERIA: RCTs reporting the analgesic effects of carbamazepine. DATA COLLECTION AND ANALYSIS: Two authors independently extracted results and scored for quality. Numbers needed to treat to benefit (NNT) or harm (NNH) with 95% confidence intervals (CI) were calculated from dichotomous data for effectiveness, adverse effects and adverse event withdrawal. Issues of study quality, size, duration, and outcomes were examined. MAIN RESULTS: Fifteen included studies (12 cross-over design; three parallel-group) with 629 participants.Carbamazepine was less effective than prednisolone in preventing postherpetic neuralgia following acute herpes zoster (1 study, 40 participants). No studies examined acute postoperative pain.Fourteen studies investigated chronic neuropathic pain: two lasted eight weeks, others were four weeks or less (mean 3 weeks, median 2 weeks). Five had low reporting quality. Ten involved fewer than 50 participants; mean and median maximum treatment group sizes were 34 and 29. Outcome reporting was inconsistent.Most placebo controlled studies indicated that carbamazepine was better than placebo. Five studies with 298 participants provided dichotomous results; 70% improved with carbamazepine and 12% with placebo. Carbamazepine at any dose, using any definition of improvement was significantly better than placebo (70% versus 12% improved; 5 studies, 298 participants); relative benefit 6.1 (3.9 to 9.7), NNT 1.7 (1.5 to 2.0). Four studies (188 participants) reporting outcomes equivalent to 50% pain reduction or more over baseline had a similar NNT.With carbamazepine, 66% of participants experienced at least one adverse event, and 27% with placebo; relative risk 2.4 (1.9 to 3.1), NNH 2.6 (2.1 to 3.5). Adverse event withdrawals occurred in12 of 323 participants (4%) with carbamazepine and 0 of 310 with placebo. Serious adverse events were not reported consistently; rashes were associated with carbamazepine. Five deaths occurred in patients on carbamazepine, with no obvious drug association. AUTHORS' CONCLUSIONS: Carbamazepine is effective in chronic neuropathic pain, with caveats. No trial was longer than four weeks, of good reporting quality, using outcomes equivalent to at least moderate clinical benefit. In these circumstances, caution is needed in interpretation, and meaningful comparison with other interventions is not possible.

Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults.

BACKGROUND: Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce nausea and vomiting commonly associated with migraine. OBJECTIVES: To determine the efficacy and tolerability of paracetamol (acetaminophen), alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine in adults. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 4 October 2010. SELECTION CRITERIA: We included randomised, double-blind, placebo- or active-controlled studies using self-administered paracetamol to treat a migraine headache episode, with at least 10 participants per treatment arm. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. MAIN RESULTS: Ten studies (2769 participants, 4062 attacks) compared paracetamol 1000 mg, alone or in combination with an antiemetic, with placebo or other active comparators, mainly sumatriptan 100 mg. For all efficacy outcomes paracetamol was superior to placebo, with NNTs of 12, 5.2 and 5.0 for 2-hour pain-free and 1- and 2-hour headache relief, respectively, when medication was taken for moderate to severe pain. Nausea, photophobia and phonophobia were reduced more with paracetamol than with placebo at 2 hours (NNTs of 7 to 11); more individuals were free of any functional disability at 2 hours with paracetamol (NNT 10); and fewer participants needed rescue medication over 6 hours (NNT 6).Paracetamol 1000 mg plus metoclopramide 10 mg was not significantly different from oral sumatriptan 100 mg for 2-hour headache relief; there were no 2-hour pain-free data. There was no significant difference between the paracetamol plus metoclopramide combination and sumatriptan for relief of "light/noise sensitivity" at 2 hours, but slightly more individuals needed rescue medication over 24 hours with the combination therapy (NNT 17).Adverse event rates were similar between paracetamol and placebo, and between paracetamol plus metoclopramide and sumatriptan. No serious adverse events occurred with paracetamol alone, but more "major" adverse events occurred with sumatriptan than with the combination therapy (NNH 32). AUTHORS' CONCLUSIONS: Paracetamol 1000 mg alone is an effective treatment for acute migraine headaches, and the addition of 10 mg metoclopramide gives short-term efficacy equivalent to oral sumatriptan 100 mg. Adverse events with paracetamol did not differ from placebo; "major" adverse events were slightly more common with sumatriptan than with paracetamol plus metoclopramide.

Ibuprofen with or without an antiemetic for acute migraine headaches in adults.

BACKGROUND: Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers do not seek professional help, relying instead on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce symptoms commonly associated with migraine headaches. OBJECTIVES: To determine efficacy and tolerability of ibuprofen, alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine headaches in adults. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 22 April 2010. SELECTION CRITERIA: We included randomised, double-blind, placebo- or active-controlled studies using self-administered ibuprofen to treat a migraine headache episode, with at least 10 participants per treatment arm. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and number needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. MAIN RESULTS: Nine studies (4373 participants, 5223 attacks) compared ibuprofen with placebo or other active comparators; none combined ibuprofen with a self-administered antiemetic. All studies treated attacks with single doses of medication. For ibuprofen 400 mg versus placebo, NNTs for 2-hour pain-free (26% versus 12% with placebo), 2-hour headache relief (57% versus 25%) and 24-hour sustained headache relief (45% versus 19%) were 7.2, 3.2 and 4.0, respectively. For ibuprofen 200 mg versus placebo, NNTs for 2-hour pain-free (20% versus 10%) and 2-hour headache relief (52% versus 37%) were 9.7 and 6.3, respectively. The higher dose was significantly better for 2-hour headache relief than the lower dose. Soluble formulations of ibuprofen 400 mg were better than standard tablets for 1-hour, but not 2-hour headache relief.Associated symptoms of nausea, vomiting, photophobia and phonophobia and functional disability were reduced within 2 hours, and fewer participants used rescue medication with ibuprofen compared with placebo. Similar numbers of participants experienced adverse events, which were mostly mild and transient.Ibuprofen 400 mg did not differ from rofecoxib 25 mg for 2-hour headache relief, 24-hour headache relief or use of rescue medication. AUTHORS' CONCLUSIONS: Ibuprofen is an effective treatment for acute migraine headaches, providing pain relief in about half of sufferers, but complete relief from pain and associated symptoms for only a minority. NNTs for all efficacy outcomes were better with 400 mg than 200 mg in comparisons with placebo, and soluble formulations provided more rapid relief. Adverse events were mostly mild and transient, occurring at the same rate as with placebo.

Single dose dipyrone for acute postoperative pain.

BACKGROUND: Dipyrone (metamizole) is a non-steroidal anti-inflammatory drug used in some countries to treat pain (postoperative, colic, cancer, and migraine); it is banned in others because of an association with life-threatening blood agranulocytosis. This review updates a 2001 Cochrane review, and no relevant new studies were identified, but additional outcomes were sought. OBJECTIVES: To assess the efficacy and adverse events of single dose dipyrone in acute postoperative pain. SEARCH STRATEGY: The earlier review searched CENTRAL, MEDLINE, EMBASE, LILACS and the Oxford Pain Relief Database to December 1999. For the update we searched CENTRAL, MEDLINE,EMBASE and LILACS to February 2010. SELECTION CRITERIA: Single dose, randomised, double-blind, placebo or active controlled trials of dipyrone for relief of established moderate to severe postoperative pain in adults. We included oral, rectal, intramuscular or intravenous administration of study drugs. DATA COLLECTION AND ANALYSIS: Studies were assessed for methodological quality and data extracted by two review authors independently. Summed total pain relief over six hours (TOTPAR) was used to calculate the number of participants achieving at least 50% pain relief. Derived results were used to calculate, with 95% confidence intervals, relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over six hours. Use and time to use of rescue medication were additional measures of efficacy. Information on adverse events and withdrawals was collected. MAIN RESULTS: Fifteen studies tested mainly 500 mg oral dipyrone (173 participants), 2.5 g intravenous dipyrone (101), 2.5 g intramuscular dipyrone (99); fewer than 60 participants received any other dose. All studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen, dexketoprofen, ketorolac, pethidine, tramadol, suprofen); eight used placebo controls.Over 70% of participants experienced at least 50% pain relief over 4 to 6 hours with oral dipyrone 500 mg compared to 30% with placebo in five studies (288 participants; NNT 2.4 (1.9 to 3.2)). Fewer participants needed rescue medication with dipyrone (7%) than with placebo (34%; four studies, 248 participants). There was no difference in participants experiencing at least 50% pain relief with 2.5 g intravenous dipyrone and 100 mg intravenous tramadol (70% vs 65%; two studies, 200 participants). No serious adverse events were reported. AUTHORS' CONCLUSIONS: Based on very limited information, single dose dipyrone 500 mg provides good pain relief to 70% of patients. For every five individuals given dipyrone 500 mg, two would experience this level of pain relief who would not have done with placebo, and fewer would need rescue medication, over 4 to 6 hours.

Cervico-thoracic or lumbar sympathectomy for neuropathic pain and complex regional pain syndrome.

BACKGROUND: This review is an update on 'Sympathectomy for neuropathic pain' originally published in Issue 2, 2003. The concept that many neuropathic pain syndromes (traditionally this definition would include complex regional pain syndromes (CRPS)) are "sympathetically maintained pains" has historically led to treatments that interrupt the sympathetic nervous system. Chemical sympathectomies use alcohol or phenol injections to destroy ganglia of the sympathetic chain, while surgical ablation is performed by open removal or electrocoagulation of the sympathetic chain, or minimally invasive procedures using thermal or laser interruption. OBJECTIVES: To review the evidence from randomised, double blind, controlled trials on the efficacy and safety of chemical and surgical sympathectomy for neuropathic pain. Sympathectomy could be compared with placebo (sham) or other active treatment. SEARCH STRATEGY: We searched MEDLINE, EMBASE and The Cochrane Library to May 2010. We screened references in the retrieved articles and literature reviews, and contacted experts in the field of neuropathic pain. SELECTION CRITERIA: Randomised, double blind, placebo or active controlled studies assessing the effects of sympathectomy for neuropathic pain and CRPS. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and validity, and extracted data. No pooled analysis of data was possible. MAIN RESULTS: Only one study satisfied our inclusion criteria, comparing percutaneous radiofrequency thermal lumbar sympathectomy with lumbar sympathetic neurolysis using phenol in 20 participants with CRPS. There was no comparison of sympathectomy versus sham or placebo. No dichotomous pain outcomes were reported. Average baseline scores of 8-9/10 on several pain scales fell to about 4/10 initially (1 day) and remained at 3-5/10 over four months. There were no significant differences between groups, except for "unpleasant sensation", which was higher with radiofrequency ablation. One participant in the phenol group experienced postsympathectomy neuralgia, while two in the radiofrequency group and one in the phenol group complained of paresthaesia during needle positioning. All participants had soreness at the injection site. AUTHORS' CONCLUSIONS: The practice of surgical and chemical sympathectomy for neuropathic pain and CRPS is based on very little high quality evidence. Sympathectomy should be used cautiously in clinical practice, in carefully selected patients, and probably only after failure of other treatment options.

Pregabalin in fibromyalgia--responder analysis from individual patient data.

BACKGROUND: Population mean changes are difficult to use in clinical practice. Responder analysis may be better, but needs validating for level of response and treatment duration. A consensus group has defined what constitutes minimal, moderate, and substantial benefit based on pain intensity and Patient Global Impression of Change scores. METHODS: We obtained individual patient data from four randomised double blind trials of pregabalin in fibromyalgia lasting eight to 14 weeks. We calculated response for all efficacy outcomes using any improvement (>or= 0%), minimal improvement (>or= 15%), moderate improvement (>or= 30%), substantial improvement (>or= 50%), and extensive improvement (>or= 70%), with numbers needed to treat (NNT) for pregabalin 300 mg, 450 mg, and 600 mg daily compared with placebo. RESULTS: Information from 2,757 patients was available. Pain intensity and sleep interference showed reductions with increasing level of response, a significant difference between pregabalin and placebo, and a trend towards lower (better) NNTs at higher doses. Maximum response rates occurred at 4-6 weeks for higher levels of response, and were constant thereafter. NNTs (with 95% confidence intervals) for >or= 50% improvement in pain intensity compared with placebo after 12 weeks were 22 (11 to 870) for pregabalin 300 mg, 16 (9.3 to 59) for pregabalin 450 mg, and 13 (8.1 to 31) for pregabalin 600 mg daily. NNTs for >or= 50% improvement in sleep interference compared with placebo after 12 weeks were 13 (8.2 to 30) for pregabalin 300 mg, 8.4 (6.0 to 14) for pregabalin 450 mg, and 8.4 (6.1 to 14) for pregabalin 600 mg. Other outcomes had fewer respondents at higher response levels, but generally did not discriminate between pregabalin and placebo, or show any dose response. Shorter duration and use of 'any improvement' over-estimated treatment effect compared with longer duration and higher levels of response. CONCLUSIONS: Responder analysis is useful in fibromyalgia, particularly for pain and sleep outcomes. Some fibromyalgia patients treated with pregabalin experience a moderate or substantial pain response that is consistent over time. Short trials using 'any improvement' as an outcome overestimate treatment effects.

Topical NSAIDs for acute pain in adults.

BACKGROUND: Use of topical NSAIDs to treat acute musculoskeletal conditions is widely accepted in some parts of the world, but not in others. Their main attraction is their potential to provide pain relief without associated systemic adverse events. OBJECTIVES: To review the evidence from randomised, double-blind, controlled trials on the efficacy and safety of topically applied NSAIDs in acute pain. SEARCH STRATEGY: We searched MEDLINE, EMBASE, The Cochrane Library, and our own in-house database to December 2009. We sought unpublished studies by asking personal contacts and searching on-line clinical trial registers and manufacturers web sites. SELECTION CRITERIA: We included randomised, double-blind, active or placebo (inert carrier)-controlled trials in which treatments were administered to adult patients with acute pain resulting from strains, sprains or sports or overuse-type injuries (twisted ankle, for instance). There had to be at least 10 participants in each treatment arm, with application of treatment at least once daily. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and validity, and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. MAIN RESULTS: Forty-seven studies were included; most compared topical NSAIDs in the form of a gel, spray, or cream with a similar placebo, with 3455 participants in the overall analysis of efficacy. For all topical NSAIDs combined, compared with placebo, the number needed to treat to benefit (NNT) for clinical success, equivalent to 50% pain relief, was 4.5 (3.9 to 5.3) for treatment periods of 6 to 14 days. Topical diclofenac, ibuprofen, ketoprofen, and piroxicam were of similar efficacy, but indomethacin and benzydamine were not significantly better than placebo. Local skin reactions were generally mild and transient, and did not differ from placebo. There were very few systemic adverse events or withdrawals due to adverse events. There were insufficient data to reliably compare individual topical NSAIDs with each other or the same oral NSAID. AUTHORS' CONCLUSIONS: Topical NSAIDs can provide good levels of pain relief, without the systemic adverse events associated with oral NSAIDs, when used to treat acute musculoskeletal conditions.

Single dose oral gabapentin for established acute postoperative pain in adults.

BACKGROUND: Gabapentin is an antiepileptic drug, also used in the treatment of neuropathic pain, which is the subject of a Cochrane review, currently under revision. Its efficacy in treating established acute postoperative pain has not been demonstrated. OBJECTIVES: To assess the efficacy and safety of single dose oral gabapentin compared with placebo in established acute postoperative pain using methods that permit comparison with other analgesics. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE, and the Oxford Pain Relief Database. Additional studies were sought from reference lists of retrieved articles and reviews. Clinical trials databases were searched for unpublished studies; clinical trial reports of several unpublished studies have been made public following litigation in the US. SELECTION CRITERIA: Single oral dose, randomised, double-blind, placebo-controlled trials of gabapentin for relief of established moderate to severe postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Studies were assessed for methodological quality and data extracted by two review authors independently. Numbers of participants with at least 50% of maximum possible total pain relief (TOTPAR) or summed pain intensity difference (SPID) with gabapentin or placebo were calculated and used to derive relative benefit (RB) or risk (RR), and number-needed-to-treat-to-benefit (NNT). Numbers of participants using rescue medication, and time to its use, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. MAIN RESULTS: Four unpublished studies met inclusion criteria; in three, participants had pain following dental surgery, and one followed major orthopaedic surgery; 177 participants were treated with a single dose of gabapentin 250 mg, 21 with gabapentin 500 mg, and 172 with placebo. At least 50% pain relief over 6 hours was achieved by 15% with gabapentin 250 mg and 5% with placebo; giving a RB of 2.5 (95% CI 1.2 to 5.0) and an NNT of 11 (6.4 to 35). Significantly fewer participants needed rescue medication within 6 hours with gabapentin 250 mg than with placebo; NNT to prevent use 5.8. About one third of participants reported adverse events with both gabapentin 250 mg and placebo. No serious adverse events occurred with gabapentin. AUTHORS' CONCLUSIONS: Gabapentin 250 mg is statistically superior to placebo in the treatment of established acute postoperative pain, but the NNT of 11 for at least 50% pain relief over 6 hours with gabapentin 250 mg is of limited clinical value and inferior to commonly used analgesics. Gabapentin 250 mg is not clinically useful as a stand-alone analgesic in established acute postoperative pain, though this is probably the first demonstration of analgesic effect of an antiepileptic in established acute pain.