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Newswise Philadelphia, June 30, 2014 In the first genome-wide analysis of postsurgical pain in children, pediatric researchers identified variations in genes that affect a childs need for pain-control drugs. The findings suggest that at some point physicians may calibrate pain-medication dosages according to a childs individual genetic makeup.

Although this research is only a first step for our team, it provides tremendous new insight into the biological mechanisms and brings us a little closer to personalizing medicine for pain control, said Scott D. Cook-Sather, M.D., a pediatric anesthesiologist at The Childrens Hospital of Philadelphia (CHOP). He is co-first author with CHOP statistician Jin Li, Ph.D., and is the corresponding author of the study.

Cook-Sather and colleagues published the study online June 9 in the journal Pain. He collaborated with Hakon Hakonarson, M.D., Ph.D., director of CHOPs Center for Applied Genomics, and the senior author of the study.

The study team performed a genome-wide association study (GWAS) of more than 600 children between ages 4 and 18 who had tonsils and adenoids removed in day surgery procedures. The retrospective study analyzed whether gene variants were associated with the need for higher or lower than average dosages of morphine for pain control. The researchers also analyzed genetic links to postoperative pain scores.

The GWAS identified one gene location linked to increased morphine requirement: the TAOK3 locus, a site not previously linked to morphine sensitivity. Genes within the TAOK3 locus carry the code for a protein with a key role in signal transduction for many cell types, including neurons involved with transmitting the sensation of pain.

It makes sense that genes related to signaling systems would modify how patients feel pain and respond to analgesics, said Cook-Sather. Follow-up studies are necessary to identify the fundamental neurobiology and details of the mechanisms involved.

While scientists already know that morphine works by binding to specific opioid receptors in the nervous system, added Cook-Sather, we dont know exactly why there is, in this setting, a tenfold variation in how much morphine patients require for pain relief. The study team found that two single-base gene variants at the TAOK3 locus were associated with approximately 8 percent of that tenfold variance in morphine requirement, comparable to that portion of the variance associated with age, body mass and overall health status combined.

Cook-Sather explained that multiple genes are assumed to contribute to these analgesic effects, and that further investigations, with larger numbers of patients, are needed to understand and prioritize the full array of genes that modify morphine response.

Read the rest here:
Gene Variants Found That Increase Pain Sensation After Common Childhood Surgery

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