Gene-to-gene Interactions Regulate Endogenous Pain Modulation in Fibromyalgia Patients and Healthy Controls-antagonistic Effects Between Opioid and Serotonin-related Genes

Overview

Journal Pain

Specialties Neurology
Psychiatry

Date 2017 Mar 11

PMID 28282362

Citations 29

Authors

Jeanette Tour

Monika Lofgren

Kaisa Mannerkorpi

Bjorn Gerdle

Anette Larsson

Annie Palstam

Indre Bileviciute-Ljungar

Jan Bjersing

Ingvar Martin

Malin Ernberg

Martin Schalling

Eva Kosek

Affiliations

Soon will be listed here.

Abstract

Chronic pain is associated with dysfunctional endogenous pain modulation, involving both central opioid and serotonergic (5-HT) signaling. Fibromyalgia (FM) is a chronic pain syndrome, characterized by widespread musculoskeletal pain and reduced exercise-induced hypoalgesia (EIH). In this study, we assessed the effects of 3 functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls. Subjects were genotyped regarding the mu-opioid receptor (OPRM1) gene (rs1799971), the serotonin transporter (5-HTT) gene (5-HTTLPR/rs25531), and the serotonin-1a receptor (5-HT1a) gene (rs6296). The patients with FM had increased pain sensitivity and reduced EIH compared with healthy controls. None of the polymorphisms had an effect on EIH on their own. We found significant gene-to-gene interactions between OPRM1 x 5-HTT and OPRM1 x 5-HT1a regarding activation of EIH, with no statistically significant difference between groups. Better EIH was found in individuals with genetically inferred strong endogenous opioid signaling (OPRM1 G) in combination with weak 5-HT tone (5-HTT low/5-HT1a G), compared with strong 5-HT tone (5-HTT high/5-HT1a CC). Based on the proposed mechanisms of these genetic variants, the findings indicate antagonistic interactions between opioid and serotonergic mechanisms during EIH. Moreover, despite different baseline pain level, similar results were detected in FM and controls, not supporting an altered interaction between opioid and 5-HT mechanisms as the basis for dysfunction of EIH in patients with FM. In summary, our results suggest that, by genetic association, the mu-opioid receptor interacts with 2 major serotonergic structures involved in 5-HT reuptake and release, to modulate EIH.

Citing Articles

A Comprehensive Analysis of Fibromyalgia and the Role of the Endogenous Opioid System.

Garcia-Dominguez M Biomedicines. 2025; 13(1).

PMID: 39857749 PMC: 11762748. DOI: 10.3390/biomedicines13010165.

Endogenous Opioids and Exercise-Related Hypoalgesia: Modern Models, Measurement, and Mechanisms of Action.

Goldfarb A, Kraemer R, Baiamonte B Adv Neurobiol. 2024; 35:137-155.

PMID: 38874722 DOI: 10.1007/978-3-031-45493-6_8.

Association of OPRM1 rs1799971, HTR1B rs6296 and COMT rs4680 polymorphisms with clinical phenotype among women with fibromyalgia.

Fernandez-de-Las-Penas C, Ambite-Quesada S, Fernandez-Mendez L, Jimenez-Antona C, Gomez-Calero C, Pocinho R Sci Rep. 2024; 14(1):11273.

PMID: 38760456 PMC: 11101407. DOI: 10.1038/s41598-024-62240-7.

Effects of functional polymorphisms of opioid receptor mu 1 and catechol-O-methyltransferase on the neural processing of pain.

Cheong Y, Lee S, Okazawa H, Kosaka H, Jung M Psychiatry Clin Neurosci. 2024; 78(5):300-308.

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