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The Influence of Gene Polymorphism OPRM1 118A/G on the Perception of Pain and Pharmacodynamics of Narcotic Analgesics

https://doi.org/10.15360/1813-9779-2014-1-58-67

Abstract

The polymorphism of μ-opioid receptor is one of the most studied polymorphisms that affect the activity of narcotic analgesics. Despite that there are a large number of publications dealing with the problem, the obtained results are not being currently used in clinical practice. The purpose of this review is to describe the impact of this polymorphism on the perception of pain and sensitivity to narcotic analgesics. It is shown that patients with the G118G genotype of μ-opioid receptor are tolerant to narcotic analgesics and need a larger dose to achieve the desired effect than that in normal genotype. At the same time, the likelihood of side effects associated with the use of narcotic analgesics does not significantly differ between the carriers of normal genotype and those of the A118G, G118G genotypes.

About the Authors

V. M. Zhenilo
Department of Pharmacology and Clinical Pharmacology, Rostov State Medical University, RostovonDon
Russian Federation


O. A. Makharin
Department of Pharmacology and Clinical Pharmacology, Rostov State Medical University, RostovonDon
Russian Federation


References

1. Дугиева М.З., Свиридов С.В., Слепцова Н.И., Морозова К.В. Факторы риска развития длительного болевого синдрома после гинекологических операций. Общая реаниматология. 2012; 8 (5): 56—60.

2. Мороз В.В., Смелая Т.В., Голубев А.М., Сальникова Л.Е. Генетика и медицина критических состояний: от теории к практике. Общая реаниматология. 2012; 8 (4): 5—12.

3. Осипова Н.А. Послеоперационное обезболивание в России: клинические и организационные аспекты. Общая реаниматология. 2013; 9 (4): 5—10.

4. Ершов А.В., Долгих В.Т., Долгих Т.И., Морозов С.В., Орлов Ю.П., Рейс А.Б. Мутация Лейдена и течение острого панкреатита тяжёлой степени. Общая реаниматология. 2013; 9 (6): 36—44.

5. Benyamin R., Trescot A.M., Datta S., Buenaventura R., Adlaka R., Sehgal N., Glaser S.E., Vallejo R. Opioid complications and side effects. Pain Physician. 2008; 11 (Suppl 2): S105—S120. PMID: 18443635

6. Højsted J., Sjøgren P. Addiction to opioids in chronic pain patients: a literature review. Eur. J. Pain. 2007; 11 (5): 490—518. http://dx.doi.org/10. 1016/j.ejpain.2006.08.004. PMID: 17070082

7. Волчков В.А., Игнатов Ю.Д., Страшнов В.И. Болевые синдромы в анестезиологии и реаниматологии. М.: МЕДпресс-Информ; 2006: 320.

8. Allegri M., De Gregori M., Niebel T., Minella C., Tinelli C., Govoni S., Regazzi M., Braschi A. Pharmacogenetics and postoperative pain: a new approach to improve acute pain management. Minerva Anestesiol. 2010; 76 (11): 937—944. PMID: 21102389

9. Glare P.A., Walsh T.D. Clinical pharmacokinetics of morphine. Ther. Drug Monit. 1991; 13 (1): 1—23. http://dx.doi.org/10.1097/00007691-199101000-00001. PMID: 2057987

10. Macintyre P.E., Jarvis D.A. Age is the best predictor of postoperative morphine requirements. Pain. 1996; 64 (2): 357—364. http://dx.doi.org/10. 1016/0304-3959(95)00128-X. PMID: 8740614

11. Cepeda M.S., Farrar J.T., Roa J.H., Boston R., Meng Q.C., Ruiz F., Carr D.B., Strom B.L. Ethnicity influences morphine pharmacokinetics and pharmacodynamics. Clin. Pharmacol. Ther. 2001; 70 (4): 351—361. http://dx.doi.org/10.1067/mcp.2001.118632. PMID: 11673751

12. Ozalp G., Sarioglu R., Tuncel G., Aslan K., Kadiogullari N. Preoperative emotional states in patients with breast cancer and postoperative pain. Acta Anaesthesiol. Scand. 2003; 47 (1): 26—29. PMID: 12492793

13. Aubrun F., Salvi N., Coriat P., Riou B. Sex- and age-related differences in morphine requirements for postoperative pain relief. Anesthesiology. 2005; 103 (1): 156—160. http://dx.doi.org/10.1097/00000542-200507000-00023. PMID: 15983468

14. Шнайдер Н.А. Новый взгляд на проблему послеоперационной когнитивной дисфункции. Острые и неотложные состояния в практике врача. 2008; 5—6: 64—67.

15. Яхно Н.Н., Кукушкин М.Л., Подчуфарова Е.В. О дисфункциональном механизме хронической боли. Мат-лы 18-ой Рос. науч.-практ. конф. «Хроническая боль». Кисловодск; 2012: 24—25.

16. Öngür D., Haddad S., Prescot A.P., Jensen J.E., Siburian R., Cohen B.M., Renshaw P.F., Smoller J.W. Relationship between genetic variation in the glutaminase gene GLS1 and brain glutamine/glutamate ratio measured in vivo. Biol. Psychiatry. 2011; 70 (2): 169—174. http://dx.doi.org/10. 1016/j.biopsych.2011.01.033. PMID: 21457947

17. Jovanovic H., Perski A., Berglund H., Savic I. Chronic stress is linked to 5-HT1A receptor changes and functional disintegration of the limbic networks. Neuroimage. 2011; 55 (3): 1178—1188. http://dx.doi.org/10.1016/j.neuroimage.2010.12.060. PMID: 21211567

18. Kosek E., Jensen K., Lonsdorf T., Schalling M., Ingvar M. Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans. Mol. Pain. 2009; 5: 37. http://dx.doi.org/10.1186/1744-8069-5-37. PMID: 19570226

19. Пшенникова М.Г., Попкова Е.В., Смирнова Е.С., Кукушкин М.Л. Изменение устойчивости к развитию невропатического болевого синдрома на фоне стресса у крыс различных генетических линий: роль катехоламинов. Мат-лы 18-ой Рос. науч.-практ. конф. «Хроническая боль». Кисловодск; 2012: 22—23.

20. Nicholl B.I., Holliday K.L., Macfarlane G.J., Thomson W., Davies K.A., O’Neill T.W., Bartfai G., Boonen S., Casanueva F., Finn J.D., Forti G., Giwercman A., Huhtaniemi I.T., Kula K., Punab M., Silman A.J., Vanderschueren D., Wu F.C., McBeth J.; European Male Ageing Study Group. No evidence for a role of the catechol-O-methyltransferase pain sensitivity haplotypes in chronic widespread pain. Ann. Rheum. Dis. 2010; 69 (11): 2009—2012. http://dx.doi.org/10.1136/ard.2009.

21. PMID: 20570835

22. Shabalina S.A., Zaykin D.V., Gris P., Ogurtsov A.Y., Gauthier J., Shibata K., Tchivileva I.E., Belfer I., Mishra B., Kiselycznyk C., Wallace M.R.,Staud R., Spiridonov N.A., Max M.B., Goldman D., Fillingim R.B., Maixner W., Diatchenko L. Expansion of the human mu-opioid receptor gene architecture: novel functional variants. Hum. Mol. Genet. 2009; 18 (6): 1037—1051. http://dx.doi.org/10.1093/hmg/ddn439. PMID: 19103668

23. Pasternak G.W. Molecular insights into mu opioid pharmacology: From the clinic to the bench. Clin. J. Pain. 2010; 26 (Suppl 10): S3—S9. http://dx.doi.org/10.1097/AJP.0b013e3181c49d2e. PMID: 20026962

24. Huang P., Chen C., Mague S.D., Blendy J.A., Liu-Chen L.Y. A common single nucleotide polymorphism A118G of the μ opioid receptor alters its N glycosylation and protein stability. Biochem. J. 2012; 441 (1): 379—386. http://dx.doi.org/10.1042/BJ20111050. PMID: 21864297

25. Bond C., LaForge K.S., Tian M., Melia D., Zhang S., Borg L., Gong J., Schluger J., Strong J.A., Leal S.M., Tischfield J.A., Kreek M.J., Yu L. Single-nucleotide polymorphism in the human mu opioid receptor genealters beta-endorphin binding and activity: possible implications for opiate addiction. Proc. Natl. Acad. Sci. USA. 1998; 95 (16): 9608—9613. PMID: 9689128

26. Befort K., Filliol D., Decaillot F.M., Gaveriaux-Ruff C., Hoehe M.R., Kieffer B.L. A single nucleotide polymorphic mutation in the human mu-opioid receptor severely impairs receptor signaling. J. Biol. Chem. 2001; 276 (5): 3130—3137. PMID: 11067846

27. Beyer A., Koch T., Schröder H., Schulz S., Höllt V. Effect of the A118G polymorphism on binding affinity, potency and agonist-mediated endocytosis, desensitization, and resensitization of the human mu-opioid receptor. J. Neurochem. 2004; 89 (3): 553—560. http://dx.doi.org/10.1111/j.1471-4159.2004.02340.x. PMID: 15086512

28. Kroslak T., Laforge K.S., Gianotti R.J., Ho A., Nielsen D.A., Kreek M.J. The single nucleotide polymorphism A118G alters functional properties of the human mu opioid receptor. J. Neurochem. 2007; 103 (1): 77—87. http://dx.doi.org/10.1111/j.1471-4159.2007.04738.x. PMID: 17877633

29. Oertel B.G., Kettner M., Scholich K., Renné C., Roskam B., Geisslinger G., Schmidt P.H., Lötsch J. A common human micro-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—6535. http://dx.doi.org/10.1074/jbc.M807030200. PMID: 19116204

30. Ray R., Ruparel K., Newberg A., Wileyto E.P., Loughead J.W., Divgi C., Blendy J.A., Logan J., Zubieta J.K., Lerman C. Human Mu Opioid Receptor (OPRM1 A118G) polymorphism is associated with brain mu-opioid receptor binding potential in smokers. Proc. Natl. Acad. Sci. USA. 2011; 108 (22): 9268—9273. http://dx.doi.org/10.1073/pnas.1018699108. PMID: 21576462

31. Luo X., Kranzler H.R., Zhao H., Gelernter J. Haplotypes at the OPRM1 locus are associated with susceptibility to substance dependence in European-Americans. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2003; 120B (1): 97—108. PMID: 12815747

32. Hoehe M.R., Köpke K., Wendel B., Rohde K., Flachmeier C., Kidd K.K., Berrettini W.H., Church G.M. Sequence variability and candidate gene analysis in complex disease: association of mu opioid receptor gene variation with substance dependence. Hum. Mol. Genet. 2000; 9 (19): 2895—2908. PMID: 11092766

33. Pang G.S., Wang J., Wang Z., Goh C., Lee C.G. The G allele of SNP E1/A118G at the mu-opioid receptor gene locus shows genomic evidence of recent positive selection. Pharmacogenomics. 2009; 10 (7): 1101—1109. http://dx.doi.org/10.2217/pgs.09.63. PMID: 19604083

34. Oertel B.G., Doehring A., Roskam B., Kettner M., Hackmann N., Ferreirós N., Schmidt P.H., Lötsch J. Genetic epigenetic interaction modulates м-opioid receptor regulation. Hum. Mol. Genet. 2012; 21 (21): 4751—4760. http://dx.doi.org/10.1093/hmg/dds314. PMID: 22875838

35. Johnson A.D., Zhang Y., Papp A.C., Pinsonneault J.K., Lim J.E., Saffen D., Dai Z., Wang D., Sadée W. Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues. Pharmacogenet. Genomics. 2008; 18 (9): 781—791. http://dx.doi.org/10.1097/FPC.0b013e3283050107. PMID: 18698231

36. Wand G.S., McCaul M., Yang X., Reynolds J., Gotjen D., Lee S., Ali A. The mu-opioid receptor gene polymorphism (A118G) alters HPA axis activation induced by opioid receptor blockade. Neuropsychopharmacology. 2002; 26 (1): 106—114. PMID: 11751037

37. Piazza P.V., Le Moal M.L. Pathophysiological basis of vulnerability to drug abuse: role of an interaction between stress, glucocorticoids, and dopaminergic neurons. Annu. Rev. Pharmacol. Toxicol. 1996; 36: 359—378. http://dx.doi.org/10.1146/annurev.pharmtox.36.1.359. PMID: 8725394

38. Bailey C.P., Connor M. Opioids: cellular mechanisms of tolerance and physical dependence. Curr. Opin. Pharmacol. 2005; 5 (1): 60—68. http://dx.doi.org/10.1016/j.coph.2004.08.012. PMID: 15661627

39. Fan P., Jiang Z., Diamond I., Yao L. Up-regulation of AGS3 during morphine withdrawal promotes cAMP superactivation via adenylyl cyclase 5 and 7 in rat nucleus accumbens/striatal neurons. Mol. Pharmacol. 2009; 76 (3): 526—533. http://dx.doi.org/10.1124/mol.109.057802. PMID: 19549762

40. Narita M., Ioka M., Suzuki M., Narita M., Suzuki T. Effect of repeated administration of morphine on the activity of extracellular signal regulated kinase in the mouse brain. Neurosci. Lett. 2002; 324 (2): 97—100. http://dx.doi.org/10.1016/S0304-3940(02)00141-6. PMID: 11988336

41. Guitart X., Thompson M.A., Mirante C.K., Greenberg M.E., Nestler E.J. Regulation of cyclic AMP response element-binding protein (CREB) phosphorylation by acute and chronic morphine in the rat locus coeruleus. J. Neurochem. 1992; 58 (3): 1168—1171. http://dx.doi.org/10.1111/j.1471 4159.1992.tb09377.x. PMID: 1531356

42. Nestler E.J. Molecular neurobiology of addiction. Am. J. Addict. 2001; 10 (3): 201—217. http://dx.doi.org/10.1080/105504901750532094. PMID: 11579619

43. Nestler E.J. Common molecular and cellular substrates of addiction and memory. Neurobiol. Learn. Mem. 2002; 78 (3): 637—647. http://dx.doi.org/10.1006/nlme.2002.4084. PMID: 12559841

44. Deb I., Chakraborty J., Gangopadhyay P.K., Choudhury S.R., Das S. Single-nucleotide polymorphism (A118G) in exon 1 of OPRM1 gene causes alteration in downstream signaling by mu opioid receptor and may contribute to the genetic risk for addiction. J. Neurochem. 2010; 112 (2): 486—496. http://dx.doi.org/10.1111/j.1471-4159.2009.06472.x. PMID: 19891732

45. Fukuda K., Hayashida M., Ide S., Saita N., Kokita Y., Kasai S., Nishizawa D., Ogai Y., Hasegawa J., Nagashima M., Tagami M., Komatsu H., Sora I., Koga H., Kaneko Y., Ikeda K. Association between OPRM1 gene polymorphisms and fentanyl sensitivity in patients undergoing painful cosmetic surgery. Pain. 2009; 147 (1—3): 194—201. http://dx.doi.org/10.1016/j.pain.2009.09.004. PMID: 19783098

46. Fukuda K., Hayashida M., Ikeda K., Koukita Y., Ichinohe T., Kaneko Y. Diversity of opioid requirements for postoperative pain control following oral surgery – is it affected by polymorphism of the м-opioid receptor? Anesth. Prog. 2010; 57 (4): 145—149. http://dx.doi.org/10.2344/0003-3006-57.4.145. PMID: 21174568

47. Chou W.Y., Yang L.C., Lu H.F., Ko J.Y., Wang C.H., Lin S.H., Lee T.H., Concejero A., Hsu C.J. Association of mu opioid receptor gene polymorphism (A118G) with variations in morphine consumption for analgesia after total knee arthroplasty. Acta Anaesthesiol. Scand. 2006; 50 (7): 787—792. http://dx.doi.org/10.1111/j.1399-6576.2006.01058.x. PMID: 16879459

48. Chou W.Y., Wang C.H., Liu P.H., Liu C.C., Tseng C.C., Jawan B. Human opioid receptor A118G polymorphism affects intravenous patient-controlled analgesia morphine consumption after total abdominal hysterectomy. Anesthesiology. 2006; 105 (2): 334—337. http://dx.doi.org/10.1097/00000542-200608000-00016. PMID: 16871067

49. Zhang W., Chang Y.Z., Kan Q.C., Zhang L.R., Lu H., Chu Q.J., Wang Z.Y., Li Z.S., Zhang J. Association of human micro opioid receptor gene polymorphism A118G with fentanyl analgesia consumption in Chinese gynaecological patients. Anaesthesia. 2010; 65 (2): 130—135. http://dx.doi.org/10.1111/j.1365-2044.2009.06193.x. PMID: 20003118

50. Zhang W., Yuan J.J., Kan Q.C., Zhang L.R., Chang Y.Z., Wang Z.Y. Study of the OPRM1 A118G genetic polymorphism associated with postoperative nausea and vomiting induced by fentanyl intravenous analgesia. Minerva Anestesiol. 2011; 77 (1): 33—39. PMID: 21150856

51. Wong C.A., McCarthy R.J., Blouin J., Landau R. Observational study of the effect of mu opioid receptor genetic polymorphism on intrathecal opioid labor analgesia and post cesarean delivery analgesia. Int. J. Obstet. Anesth. 2010; 19 (3): 246—253. http://dx.doi.org/10.1016/j.ijoa.2009.09.005. PMID: 20171873

52. Женило В.М., Махарин О.А. Влияние полиморфизма м-опиоидного рецептора OPRM1 на течение тотальной внутривенной анестезии. Мат-лы 15-ой Всерос. конф. с междунар. участием «Жизнеобеспечение при критических состояниях». 18—19 ноября 2013 г. М.; 2013: 43.

53. Zhang F., Liao Q., Li L., Wang S.Y., Hu R., Tang Y.Z., Ouyang W. The correlation between post-operative fentanyl requirements and μ-opioid receptor gene A118G polymorphism in patients undergoing radical gastrectomy. Exp. Ther. Med. 2013; 5 (4): 1147—1152. PMID: 23599738

54. Sia A.T., Lim Y., Lim E.C., Goh R.W., Law H.Y., Landau R., Teo Y.Y., Tan E.C. 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; 109 (3): 520—526. http://dx.doi.org/10. 1097/ALN.0b013e318182af21. PMID: 18719451

55. Tan E.C., Lim E.C., Teo Y.Y., Lim Y., Law H.Y., Sia A.T. Ethnicity and OPRM variant independently predict pain perception and patient-controlled analgesia usage for post-operative pain. Mol. Pain. 2009; 5: 32. http://dx.doi.org/10.1186/1744-8069-5-32. PMID: 19545447

56. Lötsch J., Skarke C., Grösch S., Darimont J., Schmidt H., Geisslinger G. The polymorphism A118G of the human mu-opioid receptor gene decreases the pupil constrictory effect of morphine-6-glucuronide but not that of morphine. Pharmacogenetics. 2002; 12 (1): 3—9. PMID: 11773859

57. Janicki P.K., Schuler G., Francis D., Bohr A., Gordin V., Jarzembowski T., Ruiz-Velasco V., Mets B. A genetic association study of the functional A118G polymorphism of the human mu-opioid receptor gene in patients with acute and chronic pain. Anesth. Analg. 2006; 103 (4): 1011—1017. PMID: 17000822

58. Coulbault L., Beaussier M., Verstuyft C., Weickmans H., Dubert L., Trégouet D., Descot C., Parc Y., Lienhart A., Jaillon P., Becquemont L. Environmental and genetic factors associated with morphine response in the postoperative period. Clin. Pharmacol. Ther. 2006; 79 (4): 316—324. http://dx.doi.org/10. 1016/j.clpt.2006.01.007. PMID: 16580900

59. Zwisler S.T., Enggaard T.P., Mikkelsen S., Verstuyft C., Becquemont L., Sindrup S.H., Brosen K. Lack of association of OPRM1 and ABCB1 single-nucleotide polymorphisms to oxycodone response in postoperative pain. J. Clin. Pharmacol. 2012; 52: 234—242. PMID: 21383334

60. Klepstad P., Rakvåg T.T., Kaasa S., Holthe M., Dale O., Borchgrevink P.C., Baar C., Vikan T., Krokan H.E., Skorpen F. The 118A > G polymorphism in the human mu-opioid receptor gene may increase morphine requirements in patients with pain caused by malignant disease. Acta Anaesthesiol. Scand. 2004; 48 (10): 1232—1239. PMID: 15504181

61. Lötsch J., von Hentig N., Freynhagen R., Griessinger N., Zimmermann M., Doehring A., Rohrbacher M., Sittl R., Geisslinger G. Cross-sectional analysis of the influence of currently known pharmacogenetic modulators on opioid therapy in outpatient pain centers. Pharmacogenet. Genomics. 2009; 19 (6): 429—436. PMID: 19514130

62. Kolesnikov Y., Gabovits B., Levin A., Voiko E., Veske A. Combined catechol-O-methyltransferase and mu-opioid receptor gene polymorphisms affect morphine postoperative analgesia and central side effects. Anesth. Analg. 2011; 112 (2): 448–453. http://dx.doi.org/10.1213/ANE.0b013e318202cc8d. PMID: 21127283

63. Walter C., Lötsch J. Meta-analysis of the relevance of the OPRM1 118A > G genetic variant for pain treatment. Pain. 2009; 146 (3): 270—275. http://dx.doi.org/10.1016/j.pain.2009.07.013. PMID: 19683391

64. Romberg R.R., Olofsen E., Bijl H., Taschner P.E., Teppema L.J., Sarton E.Y., van Kleef J.W., Dahan A. Polymorphism of mu opioid receptor gene (OPRM1:c.118A > G) does not protect against opioid-induced respiratory depression despite reduced analgesic response. Anesthesiology. 2005; 102 (3): 522—530. PMID: 15731588


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Zhenilo V.M., Makharin O.A. The Influence of Gene Polymorphism OPRM1 118A/G on the Perception of Pain and Pharmacodynamics of Narcotic Analgesics. General Reanimatology. 2014;10(1):58-67. (In Russ.) https://doi.org/10.15360/1813-9779-2014-1-58-67

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