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The association between cyclooxygenase gene polymorphisms and acute post‐surgical pain in humans
Author(s) -
MittalParikh P.D.,
Kim H.,
Brahim J.,
Rowan J.,
Dionne R.A.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.11.079
Subject(s) - single nucleotide polymorphism , analgesic , cyclooxygenase , medicine , ketorolac , proportional hazards model , visual analogue scale , pharmacogenomics , bioinformatics , gene , anesthesia , genotype , pharmacology , biology , genetics , biochemistry , enzyme
Background Variability relating to pain sensitivity, perception and tolerance has been documented; however, the exact role of genetics in the interpretation and expression of pain is currently unknown. Given the prominent role of cyclooxygenase (COX) in the inflammatory responses to tissue injury, we examined the influence of common genetic polymorphisms of COX‐1 and COX‐2 genes on the modulation of responses to clinically induced pain in humans. Methods Patients (N=200) undergoing third molar removal provided ratings of pain intensity every 20 minutes postoperatively using a 10 cm visual analog scale (VAS). Upon patient request at the onset of moderate‐severe pain, an NSAID (ketorolac) was administered. The effect of genetic variation was investigated with 5 single nucleotide polymorphisms (SNPs) in the COX‐1 gene and 9 SNPs in the COX‐2 gene. Results COX‐2 gene SNPs, including promoter variant −765G>C, show significant association for time to onset of post‐operative pain and analgesic onset time (ANOVA, p<.05). Slight but significant (3.4 ‐ 4.8%) variation in post‐operative pain measures can be attributed to these SNPs. We did not detect any influence of individual SNPs in the COX‐1 gene on pain in this clinical model. Conclusions COX‐2 gene polymorphisms contribute to post‐operative pain responses and may explain variation in pain responses between individuals following tissue injury and during COX‐2 mediated acute inflammation. Clinical Pharmacology & Therapeutics (2005) 77 , P20–P20; doi: 10.1016/j.clpt.2004.11.079