Is the antinociceptive effect of fentanyl related to the genotype?

Objective: Opioids produce their clinical effects mainly through É -opioid receptors. Polymorphisms in the human OPRM1 gene, which encodes the É -opioid receptors, may be associated with the clinical effects of opioid analgesics. The aims of the present study were to evaluate whether any of five common single nucleotide polymorphisms (SNPs) of the OPRM1 gene could affect the antinociceptive effect of fentanyl. Methods: Following institutional approval and informed consent, enrolled in the study were 108 consecutive patients (age 18-45 yr, 40 males and 68 females) scheduled to undergo sagittal splitting ramus osteotomy. The cold pain test was preoperatively performed before and at three min after intravenous bolus injection of fentanyl at 2 É g·kg-1. We observed the latency to pain perception when the patient immersed the whole part of the right hand (just distal to the wrist) in 0 °C ice-cold water. Anesthesia was induced and maintained with propofol (TCI 3.5~5É g/ml), fentanyl, and vecuronium bromide. After induction of anesthesia, 10 ml of venous blood was sampled for preparation of DNA specimen. After emergence from anesthesia, patient-controlled analgesia (PCA) with a fentanyl-droperidol combination was commenced. Intensity of spontaneous pain was assessed at 3 and 24 h postoperatively using a visual analog pain scale. PCA fentanyl consumption during the first 24 postoperative hours were recorded. Results: and Conclusion: The antinociceptive effect of fentanyl was related to the genotype involving nucleotide at OPRM1. Fentanyl was less effective in subjects with the G allele of the OPRM1 A118G SNP than those with the A allele, and subjects with the G allele required more fentanyl for adequate postoperative pain control than those with the A allele. In the future, identifying SNPs might give us information to modulate the analgesic dosage of opioid individually for better pain control.