The placebo response: relationship to outcomes in trials of postherpetic neuralgia.

Placebo responses in controlled studies of neuropathic pain, including postherpetic neuralgia, have increased in recent years and may obscure benefits of potential treatments. Investigations of the basis of the placebo effect have revealed some of the anatomical and physiological substrates for these responses. Placebo responses are accompanied by changes in activity in brain regions involved in analgesia, pain processing, reward and emotion, and they involve neurotransmitters with well established roles in pain modulation, including opioids and cholecystokinin. These findings may eventually provide useful suggestions for limiting placebo responses in clinical trials as identification of the cues that contribute to placebo responses could conceivably permit their avoidance in the design of clinical studies. Analyses of the characteristics of clinical trials in neuropathic pain have revealed some factors that might also help explain the increase in placebo responses. These factors include the longer duration of contemporary trials and recruitment practices of high-enrolling study centres. In trials of patients with postherpetic neuralgia, inclusion of patients with a short duration of post-zoster pain can result in a high rate of spontaneous remission that can contribute to an apparent 'placebo response'. Future placebo-controlled trials of treatments for postherpetic neuralgia may need to consider modifications of the design and conduct of these studies to maximize the chance of obtaining valid study results.