Mechanisms of neuropathic pain and their implications for the design of clinical trials.

A mechanism-based approach to treatment is alluring, but numerous practical problems impede its implementation. Although many new therapies have entered clinical trials, and randomized controlled trials have become larger and more sophisticated, pre-trial testing of underlying pain mechanisms is almost never performed for reasons of cost, risk to subjects, time required, and validation of the techniques used. Most registration clinical trials are performed in patients with post-herpetic neuralgia and painful diabetic neuropathy, but without more information on pain mechanisms, it remains uncertain how fully results in those two disorders can be generalized to patients with other types of chronic neuropathic pain. Examples of study designs and potential solutions are presented.