Childhood pain susceptibility driven by gene variants

Childhood pain susceptibility driven by gene variants

Pain scores in children following major surgery are associated with at least two common gene variants, researchers from Geneva University Hospitals, Switzerland, reported in the journal Anesthesia & Analgesia.

The scientists claim that their study points towards a genetic component in pain response among pediatric patients. However, an Accompanying Editorial wonders how relevant this is for pain management in individual patients, as well as prior studies which looked at pain-related genes.

Gene Variants Have an Impact on Pain Scores after Surgery

Dr Chantal Mamie and team set out to determine whether a number of candidate gene variants might have a bearing on pain scores among 168 children who had to undergo either an abdominal, bone or joint surgical intervention.

The pediatric patients and their biological parents were tested for polymorphisms (variant forms) of six separate genes which had previously been reported as possibly having an impact on pain scores.

They then compared each child's genetic results with their pain scores. The hospital routinely monitors pain scores during the 24-hour post-surgical recovery period. During those 24 hours, the kids had access to strong opioid pain relievers.

Clinically meaningful increases in pain scores were associated with variants of two genes. They defined clinically meaningful increases in pain scores when a child scored at least four peaks of six points (on a ten point scale) during that 24-hour period. After taking into account factors which might influence their findings, the researchers found that:

  • The children with a specific variant of the gene ABCB1 had a pain score 4.5 times higher than those without the gene variant. ABCB1 affects how opioid drugs are transported to the CNS (central nervous system).
  • The children with a certain variant of the OPRM gene had pain scores 3.5 times higher than those with no gene variants. OPRM is a key target receptor for opioid binding.
Even after making adjustments for inheritance from parents, the associations with the OPRM and ABCB1 variants "remained significant". A more subtle, subclinical effect on pain scores was observed with gene variants NTRK and COMT.

Gene variants had no effect on the use of pain drugs

The authors were surprised to find that the gene variants bore no relation to the total dosage of opioid medications that were administered, even though they affected pain scores. The dosage of patient-controlled analgesia provides a vital objective measure of pain and pain control post-surgery.

Dr. Mamie wrote "The present results are plausible given the known functionality of the candidate genes, and are consistent with the findings in adults."

There has been abundant research on how genes play a role in pain intensity among adults. "This first but small cohort study provides clues to further explore the genetic foundations of pediatric pain."

Inheritance of Pain Susceptibility and Opioid Responsiveness is not so Simple and Predictable

Drs Debra Schwinn and Ruth Landau from the University of Washington, Seattle, in an Accompanying Editorial explained that ten years ago scientists thought that the discovery of how genes affect our perception of pain and opioid responses would rapidly play a major role in individualizing post-surgical pain control.

However, study after study have shown that the situation is much more complex. The inheritance of pain susceptibility and opioid responsiveness is "probably less straightforward and predictable than previously foreseen."

Phenotype matters more than genotype - as gene variants have virtually no effect on pain medication dosage, the authors suggest that the genotype (the presence of gene variants) matters less than phenotype (how those genes are expressed in the patient).

As the associations are extremely complex, the authors concluded that "Tailoring opioid analgesia based on selective genotyping is unlikely to occur anytime soon."

Australian and Austrian scientists claim to have discovered a network map of genes involved in pain perception.

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