COMT and OPRM1 Polymorphisms and Their Effect on Post-Operative Pain in Children

Inadequately treated pain in children undergoing surgery is a major concern for health providers. Recent evidence indicates that pain sensitivity differs among races and ethnicities and genetic makeup. Catechol-O-methyltransferase (COMT) polymorphisms (rs6269, rs4633, rs4818 and rs4680) which are inherited together in different phenotypes influence clinical presentations and responses to pain.

A118G single-nucleotide polymorphism (SNP) in the mu-opioid receptor1 (OPRM1) gene is associated with differences in pain perception and opioid requirements. The effect of genome variations in the COMT gene and in the OPRM1 on postoperative pain perception and morphine analgesia in children needs further exploration. The main objective of this study was to investigate whether the OPRM1 and COMT SNPs influence postoperative pain scores in children between the ages of 8 and 18 undergoing orthopedic, abdominal, thoracic, and plastic surgeries. Secondary objective includes assessing whether OPRM1 and COMT SNPs influence postoperative sedation score, intraoperative and postoperative opioid requirements, length of stay in the post anesthesia care unit (PACU), and signs of respiratory depression (RD) and postoperative nausea and vomiting (PONV).

Methodology: A prospective cohort genotype-blinded observational study will be conducted. A convenience sample of 200 children between the ages of 8-18 undergoing orthopedic, abdominal, thoracic, and plastic surgeries will be recruited from the American University of Beirut Medical Center (AUBMC). The primary outcome of the study is the post operative pain score in PACU.

Secondary outcomes include the postoperative sedation score, intraoperative and postoperative opioid requirements, length of stay in the PACU, and signs of RD and PONV. To test the hypothesis that COMT and OPRM1 SNPs are associated with postoperative analgesia outcomes in children, SPSS version 29 will be used. Allelic and genotype frequencies will be examined by the Hardy-Weinberg equilibrium (HWE) test. To analyze the association between the different genetic variations and the outcomes, bivariate analysis will be performed. Variables measured over time will be compared between the groups using an exploratory mixed model analysis. Time to first post-operative opioid requirement will be analyzed using the survival analysis Kaplan Meier curve. Such understanding will pave the way for individual tailoring and optimization of pain assessment and management in children undergoing orthopedic, abdominal, thoracic, and plastic surgical procedures.

Inclusion criteria

• All children 8 years to 18 years
• Undergoing orthopedic, abdominal, thoracic, and plastic surgeries
• American Society of Anesthesiologists classification (ASA) I-II-III

Exclusion criteria

• Children with schizoid personality disorders, phobias, and anxiety
• Patients with neuropathic pain associated with surgeries requiring surgical treatment.
• Children presented with all types of depressive disorders, atypical bipolar disorder, or a suspicion of substance abuse.
• American Society of Anesthesiologists classification (ASA) ≥IV
• All patients receiving regional anesthesia, local blocks, epidural and caudal blocks.