Original Articles Open access

Does human serotonin-1A receptor polymorphism (rs6295) code for pain and associated symptoms in fibromyalgia syndrome?

Authors

Published
19 April 2021
Section
Original Articles
Pages
24-31

Abstract

Genetic predisposition may play an important role in the development of fibromyalgia syndrome (FMS). Serotonin is known to be involved in pain modulation and serotonin-1A receptor plays a considerable role in determining the central 5-HT tone. Consequently, variation in 5-HT1A receptor gene (HTR1A) may be responsible for inter-individual variability in pain sensitivity and other clinical symptoms of FMS. Therefore, the objectives of this research work were to study the gene polymorphism of 5-HTR1A gene and to explore the correlation between rs6295 genotype (−1019C/G HTR1A) and duration of pain, pain intensity and pain related depression and anxiety, if any, in FMS. 5-HTR1A genotype for the C(-1019)G polymorphism was typed in 62 patients with FMS and 42 healthy subjects. Present pain intensity, components of pain and pain related depression and anxiety were assessed using the numerical pain rating scale, McGill pain questionnaire and Hamilton depression and anxiety rating scale respectively. 5-HTR1A gene was represented by three different genotypes, homozygous C/C, heterozygous C/G and homozygous G/G. Analysis of the 5-HTR1A gene showed a frequency of 58%, 31% and 11% for the C/C, C/G and G/G genotypes, respectively in FMS group. This proportion was 69%, 23% and 8% in healthy subjects. No significant correlation was observed between 5-HTR1A gene polymorphism and pain and related symptoms in FMS patients. To the best of our knowledge this is the first study which investigated the correlation between the 5-HTR1A gene polymorphism and pain intensity, the affective component of pain, pain related depression and anxiety in FMS.

References

  1. Son CN, Kim SH, Chang HW, Kim JM. A neurometabolite study of chronic daily headache in patients with systemic lupus erythematosus using magnetic resonance spectroscopy: comparison with fibromyalgia patients and healthy controls. Korean J Intern Med. 2016; 31: 1171-7. DOI: https://doi.org/10.3904/kjim.2015.196
  2. Buskila, D, Sarzi-Puttini, P, Ablin, JN. The genetics of fibromyalgia syndrome. Pharmacogenomics. 2007; 8: 67-74. DOI: https://doi.org/10.2217/14622416.8.1.67
  3. Russell IJ, Vaeroy H, Javors M, Nyberg F. Cerebrospinal fluid biogenic amine metabolites in fibromyalgia/fibrositis syndrome and rheumatoid arthritis. Arthritis Rheum. 1992; 35: 550-6. DOI: https://doi.org/10.1002/art.1780350509
  4. Lucki I. The spectrum of behaviors influenced by serotonin. Biol Psychiat. 1998; 44: 151-62. DOI: https://doi.org/10.1016/S0006-3223(98)00139-5
  5. Lemonde S, Turecki G, Bakish D, et al. Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. J Neurosci. 2003; 23:8788-99. DOI: https://doi.org/10.1523/JNEUROSCI.23-25-08788.2003
  6. Barnes NM, Sharp T. A review of central 5-HT receptors and their function. Neuropharmacology. 1999; 38: 1083-152. DOI: https://doi.org/10.1016/S0028-3908(99)00010-6
  7. Goldberg HL, Finnerty RJ. The comparative efficacy of buspirone and diazepam in the treatment of anxiety. Am J Psychiatry. 1979; 136: 1184-7. DOI: https://doi.org/10.1176/ajp.136.9.1184
  8. Kranz GS, Kasper S, Lanzenberger R. Reward and the serotonergic system. Neuroscience. 2010; 166: 1023-35. DOI: https://doi.org/10.1016/j.neuroscience.2010.01.036
  9. Parsey RV, Oquendo MA, Ogden RT, et al. Altered serotonin 1A binding in major depression: a (carbonyl-C-11)WAY100635 positron emission tomography study. Biol Psychiatry. 2006; 59: 106-13. DOI: https://doi.org/10.1016/j.biopsych.2005.06.016
  10. Sullivan GM, Ogden RT, Oquendo MA, et al. Positron emission tomography quantification of serotonin-1A receptor binding in medication-free bipolar depression. Biol Psychiatry. 2009; 66: 223-30. DOI: https://doi.org/10.1016/j.biopsych.2009.01.028
  11. Lanzenberger RR, Mitterhauser M, Spindelegger C, et al. Reduced serotonin-1A receptor binding in social anxiety disorder. Biol Psychiatry. 2007; 61: 1081-9. DOI: https://doi.org/10.1016/j.biopsych.2006.05.022
  12. Cohn JB, Rickels K. A pooled, double-blind comparison of the effects of buspirone, diazepam and placebo in women with chronic anxiety. Curr Med Res Opin. 1989; 11: 304-20. DOI: https://doi.org/10.1185/03007998909115213
  13. Wang SM, Han C, Lee SJ, et al. A review of current evidence for vilazodone in major depressive disorder. Int J Psychiatry Clin Pract. 2013; 17: 160-9. DOI: https://doi.org/10.3109/13651501.2013.794245
  14. Lemonde S, Du L, Bakish D, et al. Association of the C(-1019)G 5-HT1A functional promoter polymorphism with antidepressant response. Int J Neuropsychopharmacol. 2004; 7: 501-6. DOI: https://doi.org/10.1017/S1461145704004699
  15. Malaguti A, Rossini D, Lucca A, et al. Role of COMT, 5-HT(1A), and SERT genetic polymorphisms on antidepressant response to transcranial magnetic stimulation. Depress Anxiety. 2011; 28: 568-73. DOI: https://doi.org/10.1002/da.20815
  16. Huang YY, Battistuzzi C, Oquendo MA, et al. Human 5-HT1A receptor C(-1019)G polymorphism and psychopathology. IntJ Neuropsychopharmacol. 2004; 7: 441-51. DOI: https://doi.org/10.1017/S1461145704004663
  17. Clauw DJ. Fibromyalgia: an overview. Am J Med. 2009; 122: S3-S13. DOI: https://doi.org/10.1016/j.amjmed.2009.09.006
  18. Ruoff GE. Depression in the patient with chronic pain. J Fam Pract. 1996; 43: S25-34.
  19. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: Report of the multicenter criteria committee. Arthritis Rheum. 1990; 33: 160-72. DOI: https://doi.org/10.1002/art.1780330203
  20. Jensen MP, McFarland CA. Increasing the reliability and validity of pain intensity measurement in chronic pain patients. Pain. 1993; 55: 195-203. DOI: https://doi.org/10.1016/0304-3959(93)90148-I
  21. Melzack R. The McGill pain questionnaire: major properties and scoring methods. Pain. 1975; 1: 277-99. DOI: https://doi.org/10.1016/0304-3959(75)90044-5
  22. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959; 32: 50-5. DOI: https://doi.org/10.1111/j.2044-8341.1959.tb00467.x
  23. Koller G, Bondy B, Preuss UW, et al. The C(−1019)G 5-HT1A promoter polymorphism and personality traits: No evidence for significant association in alcoholic patients. Behav Brain Funct. 2006; 2: 7. DOI: https://doi.org/10.1186/1744-9081-2-7
  24. Hamilton, MJ. A rating scale for depression. Neurology Neurosurgery and Psychiatr. 1960; 23: 56-62. DOI: https://doi.org/10.1136/jnnp.23.1.56
  25. Ablin JN, Bar-Shira A, Yaron M, Orr-Urtreger A. Candidate-gene approach in fibromyalgia syndrome: association analysis of the genes encoding substance P receptor, dopamine transporter and alpha1-antitrypsin. Clin Exp Rheumatol. 2009; 27: S33-8.
  26. Lebe M, Hasenbring MI, Schmieder K, et al. Association of serotonin-1A and -2A receptor promoter polymorphisms with depressive symptoms, functional recovery, and pain in patients 6 months after lumbar disc surgery. Pain. 2013; 154: 377-84. DOI: https://doi.org/10.1016/j.pain.2012.11.017
  27. Ueda H, Neyama H. LPA1 receptor involvement in fibromyalgia-like pain induced by intermittent psychological stress, empathy. Neurobiol Pain. 2017; 1: 16-25. DOI: https://doi.org/10.1016/j.ynpai.2017.04.002
  28. Potvin S, Larouche A, Normand E, et al. No relationship between the ins del polymorphism of the serotonin transporter promoter and pain perception in fibromyalgia patients and healthy controls. Eur J Pain 2010; 14: 742-6. DOI: https://doi.org/10.1016/j.ejpain.2009.12.004
  29. Riering K, Rewerts C, Zieglgänsberger W. Analgesic effects of 5‐HT3 receptor antagonists. Scand J Rheumatol. 2004; 33: 19-23. DOI: https://doi.org/10.1080/03009740410006970
  30. Bondy, B, Spaeth, M, Offenbaecher, M, et al. The T102C polymorphism of the 5-HT2A-receptor gene in fibromyalgia. Neurobiol Dis.1999; 6: 433-9. DOI: https://doi.org/10.1006/nbdi.1999.0262
  31. Tander B, Gunes S, Boke O, et al. Polymorphisms of the serotonin-2A receptor and catechol-O-methyltransferase genes: a study on fibromyalgia susceptibility. Rheumatol Int. 2008; 28: 685-91. DOI: https://doi.org/10.1007/s00296-008-0525-8
  32. Tour J, Löfgren M, Mannerkorpi K, et al. Gene-to-gene interactions regulate endogenous pain modulation in fibromyalgia patients and healthy controls - antagonistic effects between opioid and serotonin-related genes. Pain. 2017; 158: 1194-203. DOI: https://doi.org/10.1097/j.pain.0000000000000896
  33. Xiao Y, Russell IJ, Liu YG. A brain-derived neurotrophic factor polymorphism Val66Met identifies fibromyalgia syndrome subgroup with higher body mass index and C-reactive protein. Rheumatol Int. 2012; 32: 2479-85. DOI: https://doi.org/10.1007/s00296-011-1990-z

Metrics

Citations and online attention from Dimensions, Altmetric and PlumX.