THE INFLUENCE OF SINGLE-NUCLEOTIDE POLYMORPHISMS OF CATECHOL-O-METHYLTRANSFERASE GENE ON THE FORMATION OF PAIN SYNDROME AND EFFECTIVENESS OF ANALGESIA IN ONCOLOGICAL PATIENTS


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Abstract

The objective is to study the effect of single-nucleotide polymorphisms (SNPs) of COMT gene on the formation and characteristics of chronic pain, level of anxiety and depression, effectiveness of analgesia in oncological patients. Material and Methods. The study includes 196 patients with oncological pathology. The formation of chronic pain syndrome was estimated in all patients one year after surgery using the assessment of pain intensity by numeric rating scale, pain questionnaire of McGill, PainDetect. Basing on the patients genotyping data the genotypes and haplotypes frequency distribution on SNPs of rs4680, rs740603, rs2097603=rs2070577, rs4633 of COMT gene was estimated. The relationship between different genotypes, haplotypes and chronic pain intensity, severity of ranking index of pain for sensor and affective characteristics on McGill scale, presence of neuropathic component of pain and anxiety was studied in all patients sample. The same analysis was carried out in order to clarify difference in morphine consumption (mg/24h) and severity of adverse side effects such as drowsiness, confusion and hallucinations. Results. It is found that after one year the pain syndrome was developed in 134 patients. It was showed that there is direct relationship between chronic pain intensity, anxiety level and presence of mutant allele on polymorphisms of rs4680 in exon and rs740603 in intron of COMT gene. There was also revealed inverse relationship between morphine requirement and presence of pointed polymorphisms in comparison with the patients who have GG genotype of these markers. Conclusion. The determination of pointed SNPs may be useful for choosing the optimal tactics of analgesia in patients with chronic oncological pain syndrome.

About the authors

Arina P. Spasova

Medical Institution of Petrozavodsk State University

Email: arina22@mail.ru
MD, PhD, Assistant Professor of Chair of X-Ray diagnostic and X-Ray treatment with course of Critical And Respiratory Medicine of Medical Institution of Petrozavodsk State University, Petrozavodsk, 185910, Russian Federation Petrozavodsk, 185910, Russian Federation

I. V Kurbatova

Institute of Biology of the Karelian Research Centre of the RAS

Petrozavodsk, 185910, Russian Federation

O. Yu Barysheva

Medical Institution of Petrozavodsk State University

Petrozavodsk, 185910, Russian Federation

G. P Tikhova

Medical Institution of Petrozavodsk State University

Petrozavodsk, 185910, Russian Federation

References

  1. Merskey H., Bogduk N. Classification of chronic pain. 2nd ed. Seattle: IASP Press, 1994.
  2. Portenoy R. K., Lesage P. Management of cancer pain. Lancet. 353(9165):1695-700.
  3. Andersen S., Skorpen F. Variation in the COMT gene: implications for pain perception and pain treatment. Pharmacogenomics. 2009; 10(4):669-84.
  4. Madadi P., Sistonen J., Silverman G., Gladdy R., Ross C.J., Carleton B.C., Carvalho J.C., Hayden M.R., Koren G. Life-threatening adverse events following therapeutic opioid administration in adults: Is pharmacogenetic analysis useful? Pain Res. Manag. 2013; 18:133-6.
  5. Khasar S.G., McCarter G., Levine J.D. Epinephrine produces β -adrenergic receptor-mediated mechanical hyperalgesia and in vitro sensitization of rat nociceptors. J. Neurophysiol. 1999; 81: 1104-12.
  6. Liang D.Y., Liao G., Wang J., Usuka J., Guo Y., Peltz G. et al. A genetic analysis of opioid-induced hyperalgesia in mice.Anesthesiology. 2006; 104:1054-62.
  7. Tchivileva I.E., Lim P.F., Smith S.B., Slade G.D., Diatchenko L., McLean S.A. et al. Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebo-controlled, crossover pilot study. Pharmacogenet. Genomics. 2010; 20:239-48.
  8. Belfer I., Wu T., Kingman A., Krishnaraju R.K., Goldman D., Max M.B. Candidate gene studies of human pain mechanisms: methods for optimizing choice of polymorphisms and sample size. Anesthesiology. 2004; 100(6):1562-72.
  9. Palmatier M.A., Kang A.M., Kidd K.K. Global variation in the frequencies of functionally different catechol-Omethyltransferase alleles. Biol. Psychiatry. 1999; 46:557-67.
  10. Chen J., Lipska B., Halim N., Ma D., Matsumoto M., Melhem S. et al. Functional Analysis of Genetic Variation in Catechol-O-Methyltransferase (COMT): Effects on mRNA, Protein, and Enzyme Activity in Postmortem Human Brain. Am. J. Hum. Genet. 2004; 75(5):807-21.
  11. Rakvåg T.T., Klepstad P., Baar C., Kvam T.M., Dale O., Kaasa S. et al. The Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene may influence morphine requirements in cancer pain patients. Pain. 2005; 116: 73-8.
  12. Rakvåg T.T., Ross J.R., Sato H., Skorpen F., Kaasa S., Klepstad P. Genetic variation in the catechol-Omethyltransferase (COMT) gene and morphine requirements in cancer patients with pain. Mol. Pain. 2008; 4:64.
  13. Ross J.R., Riley J., Taegetmeyer A.B., Sato H., Gretton S., du Bois R.M., et al. Genetic variation and response to morphine in cancer patients: catechol-O-methyltransferase and multidrug resistance-1 gene polymorphisms are associated with central side effects. Cancer. 2008; 112:1390-403.
  14. Спасова А.П., Курбатова И.В., Барышева О.Ю., Тихова Г.П. Влияние полиморфизма гена катехол-о-метилтрансферазы на эффективность обезболивания у онкологических больных. Российский журнал боли. 2016; 3-4(51):32-42
  15. Lötsch J., Weiss M., Ahne G., Kobal G., Geisslinger G. Pharmacokinetic modeling of M6G formation after oral administration of morphine in healthy volunteers. Anesthesiology. 1999; 90:1026-38.
  16. Cherny N., Ripamonti C., Pereira J., Davis C., Fallon M., McQuay H., Mercadante S., Pasternak G., Ventafridda V. Strategies to manage the adverse effects of oral morphine: An evidence-based report. J. Clin. Oncol. 2001; 19:2542-54.
  17. Vargas-Alarcón G., Fragoso J.M., Cruz-Robles D., Vargas A., Vargas A., Lao-Villadóniga J.I et al. Catechol-O-methyltransferase gene haplotypes in Mexican and Spanish patients with fibromyalgia. Arthritis. Res. Ther. 2007; 9(5): R110.
  18. Park J.W., Lee K.S., Kim J.S., Kim Y.I., Shin H.E. Genetic Contribution of Catechol-O-methyltransferase Polymorphism in Patients with Migraine without Aura. J. Clin. Neurol. 2007; 3(1): 24-30.
  19. Diatchenko L., Slade G.D., Nackley A.G., Bhalang K., Sigurdsson A., Belfer I. et al. Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum. Mol. Genet. 2005; 14:135-43.
  20. Reyes-Gibby C.C., Shete S., Rakvag T., Bhat S.V., Skorpen F., Bruera E. et al. Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain: OPRM1 and COMT gene. Pain.2007; 130:25-30.
  21. Georgea S., Wallaceb M.R., Wrightc T.W., Moserc M.W., Greenfield W.H., Brandon K. Evidence for a biopsychosocial influence on shoulder pain: Pain catastrophizing and catechol-O-methyltransferase (COMT) diplotype predict clinical pain ratings. Pain. 2008; 136(1-2):53-61.
  22. Segerstrom SC, Miller GE. Psychological stress and the human immune system: A meta-analytic study of 30 years of inquiry. Psychol. Bull. 2004; 130:601-30.
  23. Miller G.E., Cohen S., Ritchey A.K. Chronic psychological stress and the regulation of pro-inflammatory cytokines: A glucocorticoid-resistance model. Health Psychol. 2002; 21:531-41.
  24. Sephton S.E., Lush E., Dedert E.A., Floyd A.R., Rebholz W.N., Dhabhar F.S., et al. Diurnal cortisol rhythm as a predictor of lung cancer survival. Brain Behav. Immun. 2013; 30: S163-S170.
  25. Jabbi M., Kema I.P., van der Pompe G., teMeerman G.J., Ormel J., den Boer J.A. Catechol-o-methyltransferase polymorphism and susceptibility to major depressive disorder modulates psychological stress response. Psychiatr. Genet. 2007; 17:183-93.
  26. Zubieta J., Heitzeg M., Smith Y., Bueller J., Xu K., Xu Y. et al. COMT Val158Met genotype affects mu-opioid neurotransmitter responses to a pain stressor. Science. 2003; 299:1240-3.
  27. Ross J.R., Riley J., Quigley C., Welsh K.I. Clinical pharmacology and pharmacotherapy of opioid switching in cancer patients. Oncologist. 2006; 11(7):765-73.

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