Study suggests genetic component in pain response among children

At least two common gene variants are linked to "clinically meaningful" differences in pain scores in children after major surgery, reports a study in the January issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).

"[O]ur study is highly suggestive of a genetic component in pain response among children," concludes the study by Dr Chantal Mamie and colleagues of Geneva University Hospitals, Geneva, Switzerland. But an accompanying editorial question the relevance of this and previous studies of pain-related genes for management of pain in individual patients.

Gene Variants Influence Pain Scores after Surgery…
The study was designed to explore whether several "candidate" gene variants affected pain scores in a group of 168 children undergoing major surgery—either abdominal or bone and joint operations. The children and their parents were tested for variant forms ("polymorphisms") of six different genes previously reported as having a possible impact on pain.

The genetic results were compared with the children's pain scores, as routinely monitored during the 24-hour recovery period after surgery. During that time, the children had access to patient- (or parent- or nurse-controlled) analgesia with strong opioid (morphine-related) pain relievers.

Variants of two genes were related to "clinically meaningful" increases in pain scores—at least four "peak" scores higher than six (on a ten-point scale) during the 24 hours after surgery. After adjustment for other factors, the risk of elevated pain scores was 4.5 times higher for children with a specific variant of the gene ABCB1, which affects the transport of opioid drugs to the central nervous system.

Risk of elevated pain scores was 3.5 times higher for children with a certain variant of the gene OPRM, a key target receptor for opioid binding. The associations with ABCB1 and OPRM variants remained significant after adjustment for patterns of gene inheritance from parents. Variants of two additional genes affecting pain perception—NTRK and COMT—were linked to more subtle, "subclinical" effects on pain scores.

…But Have No Effect on Use of Pain Medications
Surprisingly—even though the gene variants affected pain scores—they were unrelated to the total dosage of opioid medications used. The dosage of patient-controlled analgesia provides an important objective measure of pain and pain control after surgery.

"The present results are plausible given the known functionality of the candidate genes, and are consistent with the findings in adults," Dr Mamie and colleagues write. Although there has been a wealth of research on the genetic basis of pain in adults, the researchers add, "This first but small cohort study provides clues to further explore the genetic foundations of pediatric pain."

In an accompanying editorial, Drs Debra Schwinn and Ruth Landau of University of Washington, Seattle, put the findings in perspective. A decade ago, researchers thought that the discovery of genes affecting pain perception and opioid responses would soon play an important role in "individualizing" pain control after surgery. Subsequent studies have shown that the situation is more complex, and that the inheritance of pain susceptibility and opioid responsiveness is "probably less straightforward and predictable than previously foreseen."

Especially with the lack of effect on pain medication dosage, Drs Schwinn and Landau suggest that the presence of gene variants (genotype) may be less important than the way those genes are expressed in the individual (phenotype). Because of the complexity of the associations, they conclude, "[T]ailoring opioid analgesia based on selective genotyping is unlikely to occur anytime soon."