Translational pain research: Lessons from genetics and genomics

Abstract

Pharmacological, surgical, psychological, and alternative medicine approaches for the treatment of chronic pain, including neuropathic pain, provide only partial relief for most patients, with the efficacy of existing medications often blunted by dose-limiting side effects arising from drug actions on cells outside the pain-signaling axis. The development of more effective treatments for pain--particularly chronic pain states such as neuropathic pain--has been hampered by lack of predictive animal models and biomarkers, variation in pain characteristics between patients or on a day-to-day basis for single patients, patient stratification on the basis of symptoms rather than mechanism, and a high rate of placebo responses. We discuss genetic and genomic approaches to translational pain research. We review examples of the identification and validation of human pain targets through rodent genome-wide association studies (GWAS) and global mRNA expression studies, functional screening in flies and mice, human GWAS and whole-exome sequencing studies, and the targeted candidate gene approach. These and other emerging genetic and genomic strategies are likely to facilitate the development of new, more effective pain therapeutics.