Inflammatory and Neuropathic Pain From Bench to Bedside: What Went Wrong?

Drs. Yezierski and Hansson have provided a timely, readable, scholarly and comprehensive review of preclinical pain research with insights into the reasons for frequent failures of translation. This is a must read for anyone who is serious about improving pain management. It focuses on the variety of methods for assessing pain in animals. I would add to their assessment that the Porecca group's work using conditioned place preference as a measure of 'analgesia' is actually quite promising in that they have shown cortical involvement (anterior cingulate) and also that it is more consistent with human studies than the well established, simple, efficient and relatively cheap pain threshold and reflex measures.  

I would also emphasize the importance of doing mechanistic studies in human subjects where possible. Lost from current discussions is the old-fashioned concept of accurate diagnosis (not the same as patient phenotyping by sensory abnormality). The importance of clinical diagnosis to predicting outcomes for new medications can be quite dramatic. For example, gabapentin was shown to be effective in human neuropathic pain and its congener pregabalin also turned out to be effective. The apparent selectivity of triptans and now CGRP for migraine (and cluster headache) demonstrates that patient selection and human research can be highly effective in promoting success of new treatments. Unfortunately, grants for human mechanistic research rarely survive peer review.