By: 15 August 2014
Gene variants affect pain sensation in children after surgery

In the first genome-wide analysis of post-surgical pain in children, paediatric researchers have identified variations in genes that affect a child’s need for pain-control drugs, suggesting that in the future physicians may be able to calibrate pain-medication dosages according to a child’s individual genetic make-up.

A retrospective genome-wide association study looked at more than 600 children aged between 4 and 18 who had tonsils and adenoids removed in day-surgery procedures, and analysed whether gene variants were associated with the need for higher- or lower-than-average dosages of morphine for pain control. Genetic links to post-operative pain scores were also investigated.

The study identified a single gene location linked to increased morphine requirement that has not previously been linked to morphine sensitivity. Genes within the TAOK3 locus code for a protein with a key role in signal transduction for many cell types, including the neurons involved with transmitting the sensation of pain.

“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 personalising medicine for pain control,” said author Scott Cook-Sather, paediatric anaesthesiologist at the Children’s Hospital of Philadelphia (CHOP).

“It makes sense that genes related to signalling 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,” he said, adding: “We don’t know exactly why there is, in this setting, a tenfold variation in how much morphine patients require for pain relief.”

Two single-base gene variants at the TAOK3 locus were found to be associated with approximately 8% of the tenfold variance in morphine requirement that was seen, which is comparable with the variance associated with age, body mass and overall health status combined. Multiple genes are assumed to contribute to these analgesic effects, and further investigations are needed to understand and prioritise the full array of genes that modify morphine response.

Cook-Sather, S.D., Li, J., Goebel, T.K. et al. (2014) TAOK3, a novel genome-wide association study locus associated with morphine requirement and postoperative pain in a retrospective pediatric day surgery population. Pain, published online 9 June 2014.