Micro opioid receptor A118G polymorphism and post-operative pain: opioids' effects on heterozygous patients.
The single-nucleotide-polymorphism (SNP) 118A>G in the micro-1 opioid receptor gene (OPRM1) is associated with a decrease in the analgesic effects of opioids. The aim of this study is to assess whether 118A >G polymorphism could influence the analgesic response to opioid-based postoperative pain (POP) therapy. The study consisted of two parts: section alpha, observational, included 199 subjects undergoing scheduled surgical procedures with pain management standardized on surgery invasiveness and on expected level of postoperative pain; section beta, randomized, included 41 women undergoing scheduled caesarean delivery with continuous intra-operative epidural anesthesia and post-operative analgesia (CEA). In both sections, POP was measured over 48 h (T6h-T24h-T48h) by the visual analogue scale (VAS). In section beta we also tested the responsiveness of hypothalamic-pituitary-adrenal axis (HPA) expressed by cortisol levels. In section alpha, with cluster analysis, subjects were analyzed according to their genotype: a group (no. 1) of 34 patients reporting VAS score >3 at every time lapse was identified and included only A118G carriers, while wild-type (A118A - absence of 118A>G polymorphism) patients were unevenly distributed between those with cluster no. 2 (VAS score <3 at every study steps) and those with cluster no. 3 (VAS score progressively reducing from T6h). In section beta, A118G carriers receiving epidural sufentanil had the lowest VAS scores at T24h; also in these patients, cortisol levels remained more stable, with a mild decrease at T6h. This study shows that the OPRM1 118A>G polymorphism affects postoperative pain response in heterozygous patients: they have a different postoperative pain response than patients with wild-type genes, which may affect the efficacy of the analgesic therapy.
Unit of Anesthesia and Intensive Care, University Hospital of Foggia, Foggia. Italy. antonelladecapraris@yahoo.it
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D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000704:Analysis of Variance; D002585:Cesarean Section / Q000009:adverse effects; D016000:Cluster Analysis; D017558:Elective Surgical Procedures; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007558:Italy; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D010149:Postoperative Pain / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D010641:Phenotype; D010913:Pituitary-Adrenal System / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011446:Prospective Studies; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000235:genetics*; D012720:Severity of Illness Index; D017409:Sufentanil / Q000627:therapeutic use; D013997:Time Factors; D014147:Tramadol / Q000627:therapeutic use; D016896:Treatment Outcome
D000701:Analgesics, Opioid; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D014147:Tramadol; D017409:Sufentanil; D006854:Hydrocortisone