Multiple mechanisms have been tested in pain—how can we improve the chances of success?

Abstract

Recent advances in understanding the pathophysiology of pain have led to a wealth of molecular targets for novel analgesic drugs and many clinical drug trials. There have been successes, like the gabapentinoids for neuropathic pain and calcium channel blockers for otherwise intractable pain states; and drugs which show promise in clinical trials, like nerve growth factor inhibitors and p38 kinase inhibitors. Unfortunately there have also been a number of failures. We suggest factors which might predispose to success, for example some clinical precedence for the mechanism in pain or a genetic link for the mechanism, for example a mutation linked to a pain syndrome. We also stress the importance of demonstrating molecular target engagement with a novel compound and suggest pain biomarkers which can be used for mechanistic drug profiling.