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Molecular Pain

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Open Access 01-12-2009 | Research

Ethnicity and OPRM variant independently predict pain perception and patient-controlled analgesia usage for post-operative pain

Authors: Ene-choo Tan, Eileen CP Lim, Yik-ying Teo, Yvonne Lim, Hai-yang Law, Alex T Sia

Published in: Molecular Pain | Issue 1/2009

Abstract

Background

Morphine consumption can vary widely between individuals even for identical surgical procedures. As mu-opioid receptor (OPRM1) is known to modulate pain perception and mediate the analgesic effects of opioid compounds in the central nervous system, we examined the influence of two OPRM polymorphisms on acute post-operative pain and morphine usage in women undergoing elective caesarean delivery.

Results

Data on self-reported pain scores and amount of total morphine use according to patient-controlled analgesia were collected from 994 women from the three main ethnic groups in Singapore. We found statistically significant association of the OPRM 118A>G with self-administered morphine during the first 24-hour postoperative period both in terms of total morphine (p = 1.7 × 10^-5) and weight-adjusted morphine (p = 6.6 × 10^-5). There was also significant association of this OPRM variant and time-averaged self-rated pain scores (p = 0.024). OPRM 118G homozygotes used more morphine and reported higher pain scores than 118A carriers. Other factors which influenced pain score and morphine usage include ethnicity, age and paying class.

Conclusion

Our results suggest that ethnicity and OPRM 118A>G genotype are independent and significant contributors to variation in pain perception and postoperative morphine use in patients undergoing cesarean delivery.

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Chen AC, Dworkin SF, Haug J, Gehrig J: Human pain responsivity in a tonic pain model: psychological determinants. Pain 1989,37(2):143–160. 10.1016/0304-3959(89)90126-7CrossRef

Fillingim RB: Individual differences in pain responses. Curr Rheumatol Rep 2005,7(5):342–347. 10.1007/s11926-005-0018-7CrossRef

Kim H, Neubert JK, Rowan JS, Brahim JS, Iadarola MJ, Dionne RA: Comparison of experimental and acute clinical pain responses in humans as pain phenotypes. J Pain 2004,5(7):377–384. 10.1016/j.jpain.2004.06.003CrossRef

Nielsen CS, Price DD, Vassend O, Stubhaug A, Harris JR: Characterizing individual differences in heat-pain sensitivity. Pain 2005,119(1–3):65–74. 10.1016/j.pain.2005.09.018CrossRef

Ozcan A, Tulum Z, Pinar L, Baskurt F: Comparison of pressure pain threshold, grip strength, dexterity and touch pressure of dominant and non-dominant hands within and between right-and left-handed subjects. J Korean Med Sci 2004,19(6):874–878.PubMedCentralCrossRef

Edwards RR, Ness TJ, Weigent DA, Fillingim RB: Individual differences in diffuse noxious inhibitory controls (DNIC): association with clinical variables. Pain 2003,106(3):427–437. 10.1016/j.pain.2003.09.005CrossRef

Harris RE, Williams DA, McLean SA, Sen A, Hufford M, Gendreau RM, Gracely RH, Clauw DJ: Characterization and consequences of pain variability in individuals with fibromyalgia. Arthritis Rheum 2005,52(11):3670–3674. 10.1002/art.21407CrossRef

Nielsen CS, Stubhaug A, Price DD, Vassend O, Czajkowski N, Harris JR: Individual differences in pain sensitivity: Genetic and environmental contributions. Pain 2008,136(1–2):21–9. 10.1016/j.pain.2007.06.008CrossRef

Glance LG, Wissler R, Glantz C, Osler TM, Mukamel DB, Dick AW: Racial differences in the use of epidural analgesia for labor. Anesthesiology 2007,106(1):19–25. 10.1097/00000542-200701000-00008CrossRef

10.

Ng B, Dimsdale JE, Rollnik JD, Shapiro H: The effect of ethnicity on prescriptions for patient-controlled analgesia for post-operative pain. Pain 1996,66(1):9–12. 10.1016/0304-3959(96)02955-7CrossRef

11.

Tyler DC, Pomietto M, Womack W: Variation in opioid use during PCA in adolescents. Paediatr Anaesth 1996,6(1):33–38. 10.1111/j.1460-9592.1996.tb00350.xCrossRef

12.

Chapman CR, Donaldson GW, Jacobson RC, Hautman B: Differences among patients in opioid self-administration during bone marrow transplantation. Pain 1997,71(3):213–223. 10.1016/S0304-3959(97)03355-1CrossRef

13.

Sia AT, Lim Y, Lim EC, Goh RW, Law HY, Landau R, Teo YY, Tan EC: 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. 10.1097/ALN.0b013e318182af21CrossRef

14.

Tan EC, Lim Y, Teo YY, Goh R, Law HY, Sia AT: Ethnic differences in pain perception and patient-controlled analgesia usage for postoperative pain. J Pain 2008,9(9):849–855. 10.1016/j.jpain.2008.04.004CrossRef

15.

Tan EC, Tan CH, Karupathivan U, Yap EP: Mu opioid receptor gene polymorphisms and heroin dependence in Asian populations. Neuroreport 2003,14(4):569–572. 10.1097/00001756-200303240-00008CrossRef

16.

Oertel BG, Schmidt R, Schneider A, Geisslinger G, Lotsch J: The mu-opioid receptor gene polymorphism 118A>G depletes alfentanil-induced analgesia and protects against respiratory depression in homozygous carriers. Pharmacogenet Genomics 2006,16(9):625–636. 10.1097/01.fpc.0000220566.90466.a2CrossRef

17.

Fillingim RB, Kaplan L, Staud R, Ness TJ, Glover TL, Campbell CM, Mogil JS, Wallace MR: The A118G single nucleotide polymorphism of the mu-opioid receptor gene (OPRM1) is associated with pressure pain sensitivity in humans. J Pain 2005,6(3):159–167. 10.1016/j.jpain.2004.11.008CrossRef

18.

Klepstad P, Rakvag TT, Kaasa S, Holthe M, Dale O, Borchgrevink PC, Baar C, Vikan T, Krokan HE, Skorpen F: The 118 A>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. 10.1111/j.1399-6576.2004.00517.xCrossRef

19.

Chou WY, Yang LC, Lu HF, Ko JY, Wang CH, Lin SH, Lee TH, Concejero A, Hsu CJ: 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. 10.1111/j.1399-6576.2006.01058.xCrossRef

20.

Chou WY, Wang CH, Liu PH, Liu CC, Tseng CC, Jawan B: Human opioid receptor A118G polymorphism affects intravenous patient-controlled analgesia morphine consumption after total abdominal hysterectomy. Anesthesiology 2006,105(2):334–337. 10.1097/00000542-200608000-00016CrossRef

21.

Hayashida M, Nagashima M, Satoh Y, Katoh R, Tagami M, Ide S, Kasai S, Nishizawa D, Ogai Y, Hasegawa J, et al.: Analgesic requirements after major abdominal surgery are associated with OPRM1 gene polymorphism genotype and haplotype. Pharmacogenomics 2008,9(11):1605–1616. 10.2217/14622416.9.11.1605CrossRef

22.

Campa D, Gioia A, Tomei A, Poli P, Barale R: Association of ABCB1/MDR1 and OPRM1 gene polymorphisms with morphine pain relief. Clin Pharmacol Ther 2008,83(4):559–566. 10.1038/sj.clpt.6100385CrossRef

23.

Landau R, Kern C, Columb MO, Smiley RM, Blouin JL: Genetic variability of the mu-opioid receptor influences intrathecal fentanyl analgesia requirements in laboring women. Pain 2008,139(1):5–14. 10.1016/j.pain.2008.02.023PubMedCentralCrossRef

24.

Janicki PK, 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. 10.1213/01.ane.0000231634.20341.88CrossRef

25.

Bond C, LaForge KS, Tian M, Melia D, Zhang S, Borg L, Gong J, Schluger J, Strong JA, Leal SM, et al.: Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci USA 1998,95(16):9608–9613. 10.1073/pnas.95.16.9608PubMedCentralCrossRef

26.

Kroslak T, Laforge KS, Gianotti RJ, Ho A, Nielsen DA, Kreek MJ: The single nucleotide polymorphism A118G alters functional properties of the human mu opioid receptor. J Neurochem 2007,103(1):77–87.

27.

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(38):32618–32624. 10.1074/jbc.M504942200CrossRef

28.

Beyer A, Koch T, Schroder H, Schulz S, Hollt 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. 10.1111/j.1471-4159.2004.02340.xCrossRef

29.

Ide S, Kobayashi H, Tanaka K, Ujike H, Sekine Y, Ozaki N, Inada T, Harano M, Komiyama T, Yamada M, et al.: Gene polymorphisms of the mu opioid receptor in methamphetamine abusers. Ann N Y Acad Sci 2004, 1025: 316–324. 10.1196/annals.1316.039CrossRef

30.

Gelernter J, Kranzler H, Cubells J: Genetics of two mu opioid receptor gene (OPRM1) exon I polymorphisms: population studies, and allele frequencies in alcohol- and drug-dependent subjects. Mol Psychiatry 1999,4(5):476–483. 10.1038/sj.mp.4000556CrossRef

31.

Arias A, Feinn R, Kranzler HR: Association of an Asn40Asp (A118G) polymorphism in the mu-opioid receptor gene with substance dependence: a meta-analysis. Drug Alcohol Depend 2006,83(3):262–268. 10.1016/j.drugalcdep.2005.11.024CrossRef

32.

Ready LB, Chadwick HS, Ross B: Age predicts effective epidural morphine dose after abdominal hysterectomy. Anesth Analg 1987,66(12):1215–1218. 10.1213/00000539-198712000-00002CrossRef

33.

Macintyre PE, Jarvis DA: Age is the best predictor of postoperative morphine requirements. Pain 1996,64(2):357–364. 10.1016/0304-3959(95)00128-XCrossRef

34.

Fecho K, Miller NR, Merritt SA, Klauber-Demore N, Hultman CS, Blau WS: Acute and Persistent Postoperative Pain after Breast Surgery. Pain Med 2009,10(4):708–715. 10.1111/j.1526-4637.2009.00611.xCrossRef

Title: Ethnicity and OPRM variant independently predict pain perception and patient-controlled analgesia usage for post-operative pain
Authors: Ene-choo Tan
Eileen CP Lim
Yik-ying Teo
Yvonne Lim
Hai-yang Law
Alex T Sia
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: Molecular Pain / Issue 1/2009
Electronic ISSN: 1744-8069
DOI: https://doi.org/10.1186/1744-8069-5-32

At a glance: The STEP trials

Springer Medicine

Ethnicity and OPRM variant independently predict pain perception and patient-controlled analgesia usage for post-operative pain

Abstract

Background

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Results

Conclusion

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