The effect of opioid receptor gene polymorphism (A118G) on postoperative tramadol consumption after gynecological surgery performed with a pfannenstiel incision

Abstract

Introduction: The analgesic efficacy and side effects of opioid medications show great inter-individual differences. Genetic studies have indicated that this difference is considerably associated with the relationship between opioid and receptor. Therefore, in this study it was aimed to investigate the effect of A118G polymorphism on postoperative tramadol consumption and opioid-related side-effects after gynecological surgery performed. Material and Methods: Evaluation was made of 80 patients with I-II ASA status, scheduled for gynecological surgery performed with a pfannenstiel incision under general anesthesia. Genomic DNA was extracted from the blood samples. After surgery, all of the patients were equipped with an intravenous Tramadol patient-controlled analgesia device and tramadol consumption was measured. Pain scores were measured with a numerical rating scale. All assessments were performed prior to gene analysis. In order to detect the genotype for A118G single point mutation, Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism(RFLP) methods were used. Results: The study included 80 patients were included. Of these, 60(75%) patients were detected to have homozygous 118AA(AA) genotype and 20(25%) patients to have heterozygous 118AG(AG). No patients with homozygous 118GG(GG mutant) genotype were detected. Patients were divided into 2 separate groups based on their genotypes. The postoperative total tramadol consumption and pain score in the group carrying the AG heterozygous allele were significantly higher than in the group carrying the AA homozygous allele. No statistically significant difference was detected between the groups in respect of side-effects. Conclusions: A118G polymorphism detected in the µ-opioid receptor gene has an effect on postoperative tramadol consumption.

Keywords

• Postoperative pain
• A118G polymorphism
• Tramadol
• Mu opioid receptor

References

1. Lötsch J, Geisslinger G, Tegeder I. Genetic modulation of the pharmacological treatment of pain. Pharmacol Ther 2009; 124: 168–84.
2. Hayashida M, Nagashima M, Satoh Y, et al. Analjesic requirement after majör abdominal surgery are associated with OPRM1 gene polymorphism genotype and haplotype. Pharmacogenomics 2008; 9: 1605-16.
3. Smith HS. Variations in opioid responsiveness. Pain Physician 2008; 11: 237- 48.
4. Muralidharan A, Smith MT. Pain, analgesia and genetics. J Pharm Pharmacol 2011; 63: 1387-400.
5. Ikeda K, Ide S, Han W, Hayashida M, Uhl GR, Sora I. How individual sensitivity to opiates can be predicted by gene analyses. Trends Pharmacol Sci 2005; 26: 311-7.
6. Lötsch J, Geisslinger G. Are J-opioid receptor polymorphisms important for clinical opioid therapy? Trends Mol Med 2005; 11: 82-9.
7. Smith HS. The metabolism of opioid agents and the clinical impact of their active metabolites. Clin J Pain 2011; 27: 824-38.
8. Bond C. Single-nucleotide polymorphism in the human m opioid receptor gene alters b-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci 1998; 95: 9608–13.

9. Zhang Y, Wang D, Johnson AD, Papp AC, Sadee W. Allelic expression imbalance of human [mu] opioid receptor (OPRM1) caused by variant A118G. J Biol Chem 2005; 280: 32618-24.
10. Liu YC, Wang WS. Human Mu-opioid receptor gene A118G polymorphism predicts the efficacy of tramadol/acetaminophen combination tablets (Ultracet) in oxaliplatin-induced painful neuropathy. Cancer 2012; 118: 1718-25.
11. Ginosar Y, Davidson EM, Meroz Y, Blotnick S, Shacham M, Caraco Y. Mu opioid receptor(A118G) single-nucleotide polymorphism affects alfentanil requirements for extracorporeal shock wave lithotripsy. Br J Anaesth 2009; 103: 420-7.
12. Landau R. Pharmacogenetics: implications for obstetric anesthesia. Int J Obstet Anesth 2005; 14: 316-23.
13. Caraco Y, Maroz Y, Davidson E. Variability in alfentanil analgesia maybe attributed to polymorphism in the mu-opioid receptor gene. Clin Pharmacol Ther 2001; 69: 63.
14. Klepstad P, Rakvag TT, Kaasa S, et al. The 118AOG polymorphism in the human micro-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease. Acta Anaesthesiol Scand 2004; 48: 1232–9.
15. Murphy JD, Yan D, Hanna MN, et al. Comparison of the postoperative analgesic efficacy of intravenous patientcontrolled analgesia with tramadol to intravenous patient-controlled analgesia with opioids. J Opioid Manag 2010; 6: 141-7.
16. Zhang W, Yuan JJ, Kan QC, Zhang LR, Chang YZ, Wang ZY. Study of the OPRM1 A118G genetic polymorphism associated with postoperative nausea and vomiting induced by fentanyl intravenous analgesia. Minerva Anestesiol 2011; 77: 33–9.