Science, Medicine, and the Anesthesiologist

Genetics has been shown to account for between 25% and up to 60% of pain, which can span the spectrum between pain sensitivity and tolerance, response to analgesics, and a host of psychological predisposing factors. In this cross-sectional study, 598,339 individuals enrolled in the U.S. Department of Veterans Affairs’ Million Veteran Program aiming to identify genetic loci associated with chronic pain, which was estimated by using the median of median numerical rating scale pain scores. A subgroup analysis was performed in 291,759 veterans of African, Hispanic, and European ancestry who did not have a lifetime diagnosis of opioid use disorder. They identified 126 independent genetic loci, 69 of which were previously unidentified. Pain was described as severe, moderate, and mild in 24.4%, 19.2% and 4.5%, respectively, of the full cohort, with comparable rates in the sample without opioid use disorder. Pain intensity genetically correlated with different pain phenotypes (particularly multisite pain), substance use disorders and other psychiatric characteristics, education level and cognitive traits, as well as social variables such as obesity and smoking. Drugs identified as having possible analgesic effects included anticonvulsants, psychoanaleptics, and methoxyflurane, an anesthetic agent used as an analgesic drug outside of the United States.

Take home message: This large genetic study provides clues to important molecular contributors to the experience of pain and highlights potential drug targets. Generalization to a broader population (including Asian, Native American, and nonveteran populations) and clinical studies to confirm these findings are needed.