Main Article Content
OPRM1, rs1799971, Postoperative Pain, Tramadol, Efficacy, Safety, Genotypes, Pakistani Population, Personalized Medicine
Objective: This pioneering study aims to understand the influence of genetic polymorphism identified as rs1799971 in the exon 1 of mu-opioid receptor (OPRM1) gene on the safety and efficacy of tramadol in context to postoperative pain within Pakistani population. Insights from this research may contribute to more tailored approaches to pain management in this demographic.
Study Design: Uncontrolled Cohort Pharmacogenetics Studies
Place & duration of study: Nawaz Sharif Medical College, Gujrat from March 2022- December 2022
Methods: This study was conducted within Gujrat city population in Punjab, Pakistan. Participants were genotyped for the OPRM1 (rs1799971) SNP (AA, AG, GG) using Sanger sequencing technique. Postoperative pain scores, rescue analgesic requirements, and side effects such as nausea, vomiting, and sedation were assessed at multiple time points within 24 hours post-surgery among the three OPRM1 genotypes. The data were analyzed using IBM SPSS Statistics 26, comparing pain scores and categorical variables like sedation and nausea amongst different genotypes, considering a p-value of 0.05 or less as statistically significant.
Results: The variant allele “G” was observed in 31.5% of study population with GG genotype in 11% of our study population, adhering to Hardy-Weinberg equilibrium. Patients with GG genotype reported statistically higher pain scores both at rest and on movement (<0.001 vs AA) and required more rescue analgesia in the immediate postoperative phase. However, they experienced fewer incidents of nausea, vomiting, and sedation within the initial post-surgery hours. Similarly other tramadol induced side effects were minimally observed in this set of patients.
Conclusion: This study underscores the significant influence of OPRM1(rs1799971) genotypes on efficacy and safety of tramadol in acute pain settings within the Pakistani population paving way for personalized analgesic strategies to optimize patient results
2. Peponis T, Kaafarani HMA. What Is the Proper Use of Opioids in the Postoperative Patient? Adv Surg 2017;51(1):77–87.
3. Crist RC, Berrettini WH. Pharmacogenetics of OPRM1. Pharmacology Biochemistry and Behavior 2014 Aug 1;123:25-33.
4. Doostmohammadi M, Rahimi HR. ADME and toxicity considerations for tramadol: from basic research to clinical implications. Expert Opin Drug Metab Toxicol 2020;16(7):627–40.
5. De Capraris A, Cinnella G, Marolla A, Salatto P, Da Lima S, Vetuschi P, et al. Micro opioid receptor A118G polymorphism and post-operative pain: Opioids’ effects on heterozigous patients. Int J Immunopathol Pharmacol 2011;24(4):993–1004.
6. Mura E, Govoni S, Racchi M, Carossa V, Nadia Ranzani G, Allegri M, et al. Consequences of the 118A>G polymorphism in the OPRMI gene: Translation from bench to bedside? J Pain Res.2013;6:331–53.
7. Hwang IC, Park J-YY, Myung S-KK, Ahn HY, Fukuda KI, Liao Q. OPRM1 A118G Gene Variant and Postoperative Opioid Requirement A systematic review and meta-analysis. Anesthesiology 2014 Oct 4;121(4):825–34.
8. Henker RA, Lewis A, Dai F, Lariviere WR, Meng L, Gruen GS, et al. The Associations Between OPRM1 and COMT Genotypes and Postoperative Pain, Opioid Use, and Opioid-Induced Sedation. Biol Res Nurs 2013;15(3):309–17.
9. National Center for Biotechnology Information USNL of M. The Single Nucleotide Polymorphism Database (dbSNP)- rs1799971 [Internet] 2023. Available from: https://www.ncbi.nlm.nih.gov/snp/rs1799971
10. Hong EP, Park JW. Sample Size and Statistical Power Calculation in Genetic Association Studies. Genomics Inform 2012;10(2):117.
11. Nakhaee S, Hoyte C, Dart RC, Askari M, Lamarine RJ, Mehrpour O. A review on tramadol toxicity: mechanism of action, clinical presentation, and treatment. Forensic Toxicol 2021;39(2):293–310.
12. Neskovic N, Mandic D, Marczi S, Skiljic S, Kristek G, Vinkovic H, et al. Different Pharmacokinetics of Tramadol, O-Demethyltramadol and N-Demethyltramadol in Postoperative Surgical Patients From Those Observed in Medical Patients. Front Pharmacol 2021;12(April):1–10.
13. Karcioglu O, Topacoglu H, Dikme O, Dikme O. A systematic review of the pain scales in adults: Which to use? Am J Emerg Med 2018;36(4):707–14.
14. Nisbet AT, Mooney-Cotter F. Comparsion of Selected Sedation Scales for Reporting Opioid-Induced Sedation Assessment. Pain Manag Nurs 2009;10(3):154–64.
15. Zhang P, Seth A, Fernandes H. Other Post-PCR Detection Technologies. In: Pathobiology of Human Disease: A Dynamic Encyclopedia of Disease Mechanisms. Academic Press;2014: p. 4074–88.
16. Paul AK, Smith CM, Rahmatullah M, Nissapatorn V, Wilairatana P, Spetea M, Gueven N, Dietis N. Opioid analgesia and opioid-induced adverse effects: A review. Pharmaceuticals 2021;14(11):1091.
17. Shipton EA. Reviews Tramadol — Present and Future. Anaesth Intensive Care 2000; 28 363-374 Rev. 2000;28(4):363–74.
18. Zhang X, Liang Y, Zhang N, Yan Y, Liu S, Fengxi H, et al. The relevance of the OPRM1 118A > G genetic variant for opioid requirement in pain treatment: A meta-analysis. Pain Physician 2019;22(4):331–40.
19. Khalil H, Sereika SM, Dai F, Alexander S, Conley Y, Gruen G, et al. OPRM1 and COMT Gene–Gene Interaction Is Associated With Postoperative Pain and Opioid Consumption After Orthopedic Trauma. Biol Res Nurs 2017;19(2):170–9.
20. Oertel BG, Kettner M, Scholich K, Renné C, Roskam B, Geisslinger G, et al. A Common Human mu-Opioid Receptor Genetic Variant Diminishes the Receptor Signaling Efficacy in Brain Regions Processing the Sensory Information of Pain. J Biol Chem 2009;284(10):6530–5.
21. Huang P, Chen C, Mague SD, Blendy JA, Liu-Chen LY. A common single nucleotide polymorphism A118G of the μ opioid receptor alters its N-glycosylation and protein stability. Biochem J 2012;441(1):379–86.
22. Saiz-Rodríguez M, Valdez-Acosta S, Borobia AM, Burgueño M, Gálvez-Múgica MÁ, Acero J, et al. Influence of Genetic Polymorphisms on the Response to Tramadol, Ibuprofen, and the Combination in Patients With Moderate to Severe Pain After Dental Surgery. Clin Ther 2021;43(5):e86–102.
23. Pettini E, Micaglio M, Bitossi U, De Gaudio AR, Degl’Innocenti DR, Tofani L, et al. Influence of OPRM1 Polymorphism on Postoperative Pain after Intrathecal Morphine Administration in Italian Patients Undergoing Elective Cesarean Section. Clin J Pain 2018;34(2):178–81.
24. Muriel J, Margarit C, Barrachina J, Ballester P, Flor A, Morales D, et al. Pharmacogenetics and prediction of adverse events in prescription opioid use disorder patients. Basic Clin Pharmacol Toxicol 2019 Apr 1;124(4):439–48.
25. Sia AT, Lim Y, Lim ECPP, Goh RWCC, Law HY, Landau R, et al. A118G single nucleotide polymorphism of human mu-opioid receptor gene influences pain perception and patient-controlled intravenous morphine consumption after intrathecal morphine for postcesarean analgesia. Anesthesiology 2008 Sep;109(3):520–6.
26. Kolesnikov Y, Gabovits B, Levin A, Voiko E, Veske A. Combined catechol-O-methyltransferase and μ-opioid receptor gene polymorphisms affect morphine postoperative analgesia and central side effects. Anesth Analg 2011;112(2):448–53.