January 10, 2014

A pain in the … genes

Vanderbilt researchers have discovered that variation in the gene encoding the potassium channel GIRK1 plays a role in modulating human pain perception.


Genetic variations in several genes have been linked to human pain perception and the risk for developing chronic pain. The potassium channels GIRK1 and GIRK2 are part of the signaling pathway for opioid receptors that determine the analgesia produced by medicines like morphine, but they have received little attention for their possible impact on human pain responses.

Stephen Bruehl, Ph.D., professor of Anesthesiology, and colleagues examined variation in the genes encoding GIRK1 and GIRK2 in a set of patients undergoing knee replacement surgery. They identified eight changes in GIRK2 (none in GIRK1) that were associated with post-surgical opioid medication orders, an indicator of pain severity. They developed a GIRK-related risk score (GRRS) to classify pain responses based on GIRK2 genetic variation. In follow-up studies, they found that high GRRS scores were associated with lower acute pain tolerance and higher chronic low back pain intensity.

The findings, reported in the December issue of the journal Pain, support a role for GIRK2 genetic variation in modulating pain perception.

This research was supported in part by grants from the National Institutes of Health (DA031726, NS050578, NS046694, MH071260, AG036445, GM007347). The data set used for the analyses was in part obtained from Vanderbilt University Medical Center’s BioVU, which is supported by institutional funding and by the Vanderbilt CTSA grant from the NIH (TR000445).

Send suggestions for articles to highlight in Aliquots and any other feedback about the column to aliquots@vanderbilt.edu