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Basic research indicates that systemic local-anaesthetic-type drugs that block sodium channels are effective in pain due to nerve damage. These drugs were first used as analgesics in the 1950s and they are still commonly used to try to relieve neuropathic pain and incident pain caused by cancer. As they are potentially toxic, these drugs should not be used without proven effectiveness. For these reasons, a systematic review of randomized controlled trials of systemically administered local-anaesthetic-type drugs in chronic pain was performed. Main outcomes were pain relief or pain intensity difference and adverse effects. Twenty-one reports were found, and four publications were excluded. In the remaining 17 studies (450 patients), 10 used intravenous lignocaine, two used intranasal lignocaine, four used oral mexiletine and one used oral tocainide.

The paper arises from collaborative work to explore contributions which the technology of control engineering can make to pain-control. Pain is modelled as the difference between discomfort and comfort and is measured by the frequency at which the patient presses a button. Clinical trials of an automatic pain-control system have shown that a general-purpose microcomputer can be used to control on-demand analgesia for patients recovering from major surgery.

Variability in patients' response to interventions in pain and other clinical settings is large. Many explanations such as trial methods, environment or culture have been proposed, but this paper sets out to show that the main cause of the variability may be random chance, and that if trials are small their estimate of magnitude of effect may be incorrect, simply because of the random play of chance. This is highly relevant to the questions of `How large do trials have to be for statistical accuracy?' and `How large do trials have to be for their results to be clinically valid?' The underlying control event rate (CER) and experimental event rate (EER) were determined from single-dose acute pain analgesic trials in over 5000 patients. Trial group size required to obtain statistically significant and clinically relevant (0.95 probability of number-needed-to-treat within ±0.5 of its value) results were computed using these values. Ten thousand trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to random chance alone. Most common analgesics have EERs in the range 0.4-0.6 and CER of about 0.19. With such efficacy, to have a 90% chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30-60. For clinical relevance nearly 500 patients are required in each group. Only with an extremely effective drug (EER>0.8) will we be reasonably sure of obtaining a clinically relevant NNT with commonly used group sizes of around 40 patients per treatment arm. The simulated trials showed substantial variation in CER and EER, with the probability of obtaining the correct values improving as group size increased. We contend that much of the variability in control and experimental event rates is due to random chance alone. Single small trials are unlikely to be correct. If we want to be sure of getting correct (clinically relevant) results in clinical trials we must study more patients. Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional (small) size.

Objectives:To compare the relative merits of single doses of ibuprofen and ibuprofen plus caffeine in the treatment of pain after third molar removal. Design:Randomised, double-blind, placebo-controlled, single-dose parallel-group comparison of placebo, ibuprofen 200 and 400 mg with ibuprofen 200 mg plus 50, 100 or 200 mg of caffeine. Subjects:161 patients undergoing lower third molar removal. Results:All active treatments produced significant analgesia and mood elevation compared with placebo. There was no significant difference in the effects of 200 and 400 mg of ibuprofen. Adding caffeine to 200 mg ibuprofen produced significantly more analgesic effect at 45 and 60 min than ibuprofen 200 mg alone. Ten patients reported 11 adverse effects, none in the highest caffeine dose group. Conclusions:Caffeine increased the analgesic effect of ibuprofen 200 mg, through an earlier onset of analgesic effect. This was achieved in this single dose context without problematic adverse effects.

A radioimmunoassay kit (DPC buprenorphine double antibody) was evaluated with clinical samples and samples from a drug clinic. Urine samples were collected over a 2-day period from 5 hospital in-patients receiving sublingual buprenorphine, 400 to 2000 µg/day, for the relief of chronic pain. Samples were measured before and after enzymatic hydrolysis. Urine buprenorphine concentrations were measurable at all doses studied (minimum value 5.6 ng/mL) and were greater with larger doses. The increase in concentration after hydrolysis averaged 49% and was similar for all doses studied. The authors conclude that the method has extensive cross-reactivity with glucuronides of buprenorphine and its metabolites and that samples may be analyzed without prior hydrolysis. The prevalence of buprenorphine use in 97 patients attending a drug clinic was also studied. Sixty (62%) had measurable urinary buprenorphine concentrations of 1 ng/mL or more by direct assay. The buprenorphine users were significantly younger and reported significantly greater use of opiates than nonusers.