Functional Markers of Nociceptive Processing and Central Sensitization for Pre-Clinical and Clinical Drug Development

Currently available pharmacological therapies provide inadequate relief for many patients with chronic pain. Novel drugs which are efficacious analgesics in preclinical models often have little or no clinical efficacy, but it is often not known whether the drug engaged the human target sufficiently to have a meaningful pharmacodynamic effect. To address this issue Regulatory Agencies are recommending the development and use of objective biomarkers of nociceptive processing to improve the development of drugs for chronic pain. Unfortunately, objective measures for quantifying central sensitization, a key mechanism for chronic pain, are lacking. This presentation will provide information on how psychophysical, electrophysiological and neuro-imaging biomarkers might be used to build a quantitative understanding between drug exposure and target engagement. In this presentation we will also describe back-translational biomarkers for bridging animal and human studies, and describe how the development of functional biomarkers of central sensitization could accelerate the development of novel analgesics in several ways: preclinical prediction could be improved by using translatable readouts across species; clinical Phase 1 trials could benefit from biomarkers of target engagement and from human surrogate models predictive of clinical efficacy; clinical Phase 2 and 3 studies could benefit from tools for patient stratification.