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Gene-to-gene interactions regulate endogenous pain modulation in fibromyalgia patients and healthy controls-antagonistic effects between opioid and serotonin-related genes
Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
Karolinska Institute, Sweden; Danderyd Hospital, Sweden.
University of Gothenburg, Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
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2017 (English)In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 158, no 7, 1194-1203 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS , 2017. Vol. 158, no 7, 1194-1203 p.
Keyword [en]
Chronic pain; Fibromyalgia; Exercise-induced hypoalgesia; Exercise; Pain inhibition; Functional genetic polymorphisms; 5-HTT; Serotonin transporter; OPRM1; Opioid receptor; 5-HT1a; 5-HT1a receptor
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:liu:diva-139598DOI: 10.1097/j.pain.0000000000000896ISI: 000404972200005PubMedID: 28282362OAI: oai:DiVA.org:liu-139598DiVA: diva2:1133776
Note

Funding Agencies|Swedish Rheumatism Association; Swedish Research Council [K2013-52X-22199-01-3, K2009-52P-20943-03-1, K2009-69P-21300-01-4, 10909, K2015-99X-21874-05-05]; Stockholm County Council; Health and Medical Care Executive Board of Vastra Gotaland Region; ALF-LUA at Sahlgrenska University Hospital; Linkoping University Hospital; Linkoping University; AFA Insurance; Wilhelm and Martina Lundgrens Foundation; Rune and Ulla Amlovs Trust; European Union [602919]

Available from: 2017-08-16 Created: 2017-08-16 Last updated: 2017-08-16

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Gerdle, BjörnBileviciute-Ljungar, Indre
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