The OPRM1 gene and interactions with the 5-HT1a gene regulate conditioned pain modulation in fibromyalgia patients and healthy controls.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2022
2022
Historique:
received:
24
05
2022
accepted:
27
10
2022
entrez:
7
11
2022
pubmed:
8
11
2022
medline:
10
11
2022
Statut:
epublish
Résumé
Fibromyalgia (FM) patients have dysfunctional endogenous pain modulation, where opioid and serotonergic signaling is implicated. The aim of this study was to investigate whether genetic variants in the genes coding for major structures in the opioid and serotonergic systems can affect pain modulation in FM patients and healthy controls (HC). Conditioned pain modulation (CPM), evaluating the effects of ischemic pain on pressure pain sensitivity, was performed in 82 FM patients and 43 HC. All subjects were genotyped for relevant functional polymorphisms in the genes coding for the μ-opioid receptor (OPRM1, rs1799971), the serotonin transporter (5-HTT, 5-HTTLPR/rs25531) and the serotonin 1a receptor (5-HT1a, rs6295). Results showed the OPRM1 G-allele was associated with decreased CPM. A significant gene-to-gene interaction was found between the OPRM1 and the 5-HT1a gene. Reduced CPM scores were seen particularly in individuals with the OPRM1 G*/5-HT1a CC genotype, indicating that the 5-HT1a CC genotype seems to have an inhibiting effect on CPM if an individual has the OPRM1 G-genotype. Thus, regardless of pain phenotype, the OPRM1 G-allele independently as well as with an interaction with the 5-HT1a gene influenced pain modulation. FM patients had lower CPM than HC but no group differences were found regarding the genetic effects on CPM, indicating that the results reflect more general mechanisms influencing pain modulatory processes rather than underlying the dysfunction of CPM in FM. In conclusion, a genetic variant known to alter the expression of, and binding to, the my-opioid receptor reduced a subject's ability to activate descending pain inhibition. Also, the results suggest a genetically inferred gene-to-gene interaction between the main opioid receptor and a serotonergic structure essential for 5-HT transmission to modulate pain inhibition. The results in this study highlight the importance of studying joint synergistic and antagonistic effects of neurotransmittor systems in regard to pain modulation.
Identifiants
pubmed: 36342939
doi: 10.1371/journal.pone.0277427
pii: PONE-D-22-13588
pmc: PMC9639841
doi:
Substances chimiques
Analgesics, Opioid
0
Receptor, Serotonin, 5-HT1A
112692-38-3
Receptors, Opioid, mu
0
OPRM1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0277427Informations de copyright
Copyright: © 2022 Tour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Curr Opin Anaesthesiol. 2010 Oct;23(5):611-5
pubmed: 20543676
Med Sci Sports Exerc. 2015 Jan;47(1):176-84
pubmed: 24870571
Pain. 1997 Mar;70(1):41-51
pubmed: 9106808
Pain Physician. 2019 Jul;22(4):331-340
pubmed: 31337162
Handb Clin Neurol. 2014;119:513-27
pubmed: 24365316
Pain. 1996 Dec;68(2-3):375-83
pubmed: 9121827
Clin J Pain. 2012 Sep;28(7):623-7
pubmed: 22156892
J Neurosci. 2003 Sep 24;23(25):8788-99
pubmed: 14507979
Pain. 2009 Jul;144(1-2):95-100
pubmed: 19410366
Science. 1996 Nov 29;274(5292):1527-31
pubmed: 8929413
J Biol Chem. 2012 Feb 24;287(9):6615-27
pubmed: 22232550
Neurophysiol Clin. 2021 Jun;51(3):197-208
pubmed: 33334645
Prog Neurobiol. 2009 May;88(1):17-31
pubmed: 19428959
Nat Rev Neurosci. 2004 Jul;5(7):565-75
pubmed: 15208698
Psychiatr Genet. 1999 Jun;9(2):105-6
pubmed: 10412191
Pharmacol Res. 2018 Aug;134:212-219
pubmed: 29969666
J Biol Chem. 2009 Mar 6;284(10):6530-5
pubmed: 19116204
J Pain. 2019 Apr;20(4):462-471
pubmed: 30385319
Eur J Pain. 2021 Feb;25(2):398-414
pubmed: 33064887
J Pain. 2011 Aug;12(8):875-83
pubmed: 21719351
Clin Exp Rheumatol. 2020 Jan-Feb;38 Suppl 123(1):3-8
pubmed: 32116216
Behav Brain Funct. 2006 Apr 20;2:14
pubmed: 16626484
J Pain Res. 2013 May 01;6:331-53
pubmed: 23658496
Mol Psychiatry. 2006 Mar;11(3):224-6
pubmed: 16402131
Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9608-13
pubmed: 9689128
Arthritis Rheum. 1990 Feb;33(2):160-72
pubmed: 2306288
Arthritis Rheum. 2013 Dec;65(12):3293-303
pubmed: 23982850
J Rheumatol. 2011 Jun;38(6):1113-22
pubmed: 21285161
Mol Pain. 2012 Apr 26;8:32
pubmed: 22537768
Pain. 2010 Oct;151(1):77-86
pubmed: 20621420
Arthritis Care Res (Hoboken). 2011 Nov;63 Suppl 11:S240-52
pubmed: 22588748
Pain. 2021 Nov 1;162(11):2629-2634
pubmed: 33974577
J Psychosom Res. 2002 Feb;52(2):69-77
pubmed: 11832252
J Neurosci. 2007 Sep 12;27(37):10000-6
pubmed: 17855614
Neuropsychopharmacology. 2015 Mar;40(4):957-65
pubmed: 25308352
J Pharmacol Exp Ther. 2006 Feb;316(2):892-9
pubmed: 16254131
BMC Musculoskelet Disord. 2004 Dec 09;5:48
pubmed: 15588296
J Clin Med. 2020 Apr 23;9(4):
pubmed: 32340369
J Pharmacol Exp Ther. 2003 Aug;306(2):505-14
pubmed: 12730352
Pharmacol Ther. 2009 Nov;124(2):168-84
pubmed: 19615406
Pain. 2017 Jul;158(7):1194-1203
pubmed: 28282362
Mol Pain. 2009 Jun 23;5:32
pubmed: 19545447
Arthritis Rheum. 1992 May;35(5):550-6
pubmed: 1374252
Pain. 2016 Nov;157(11):2410-2419
pubmed: 27559835
Pain. 2016 Jul;157(7):1382-1386
pubmed: 26835783
Psychophysiology. 2014 Mar;51(3):267-76
pubmed: 24354707
Lancet. 2021 May 29;397(10289):2098-2110
pubmed: 34062144
PLoS One. 2011 Mar 28;6(3):e18252
pubmed: 21464942
Semin Arthritis Rheum. 2016 Dec;46(3):319-329
pubmed: 27916278
Neuroscience. 2016 Dec 3;338:114-129
pubmed: 27291641
Clin Exp Rheumatol. 2005 Sep-Oct;23(5 Suppl 39):S154-62
pubmed: 16273800
Pain. 2016 Oct;157(10):2217-2225
pubmed: 27420606
PLoS One. 2012;7(8):e43221
pubmed: 22952650
Hum Mol Genet. 2012 Nov 1;21(21):4751-60
pubmed: 22875838
Pain. 2009 Dec;146(3):270-275
pubmed: 19683391
Scand J Rehabil Med. 1993 Sep;25(3):117-24
pubmed: 8248762
Pain. 2020 Sep 1;161(9):2079-2088
pubmed: 32379218
Mol Pain. 2009 Jul 01;5:37
pubmed: 19570226
Eur J Pain. 2010 Aug;14(7):742-6
pubmed: 20080425
Pain. 2022 Feb 1;163(2):274-286
pubmed: 34142769
J Neurosci. 2006 Feb 8;26(6):1864-71
pubmed: 16467535
Mol Brain. 2021 May 12;14(1):81
pubmed: 33980291
Pain. 1995 Jun;61(3):481-486
pubmed: 7478692
Br J Pharmacol. 2012 Mar;165(6):1956-1965
pubmed: 21950560