Genetic Study Identifies Neurotransmitter Connection Between Surgical Pain and Anxiety Sensitivity
Published July 2019 | Journal of Pain
A study of 73 adolescents undergoing spine fusion surgery has identified specific epigenetically enriched pathways that help explain a neurotransmitter connection between chronic postsurgical pain (CPSP) and anxiety sensitivity in children.
The multidisciplinary team’s analysis of 39 peripheral blood sample genes identified, respectively, 637 and 2,445 associated differentially DNA methylated positions (DMPS) that are associated with CPSP and scores on the Child Anxiety Sensitivity Index (CASI). Specifically, the findings support Gamma aminobutyric acid (GABA) hypofunction and involvement of the dopamine DARPP32 pathway (active in emotion/reward) in anxiety sensitivity and pain.
The findings “have mechanistic as well as translational implications with potential to positively impact outcomes for children undergoing surgery,” says lead author Vidya Chidambaran, MD, divisional director of perioperative pain management. Analysis of the gene-gene interaction network revealed participation of pathways in cell signaling, molecular transport, connective tissue development, metabolism, and neurologic diseases.
“The epigenetic findings point to pathways at the intersection of behavioral disorders like anxiety, and persistence of pain 10-12 months after surgery,” she explains. “Not only do they have the potential to serve as predictive biomarkers, they also suggest common environmental/external influences on these phenotypes, yielding insight into future research for potential targeted and/or individualized preventive and therapeutic strategies.”
Since the study’s July 2019 publication in the Journal of Pain, Chidambaran has received additional Cincinnati Children's and NIH funding to validate the findings in a bigger cohort and conduct longitudinal methylation studies to understand the effect of pain/opioid use on epigenetic mechanisms underlying acute to chronic pain translations. One of those will be an imaging study to correlate blood epigenetic findings with neurochemical imaging markers in the brain.
