• Jeanette Tour, Monika Löfgren, Kaisa Mannerkorpi, Björn Gerdle, Anette Larsson, Annie Palstam, Indre Bileviciute-Ljungar, Jan Bjersing, Ingvar Martin, Malin Ernberg, Martin Schalling, and Eva Kosek.
• aDepartment of Clinical Neuroscience, Osher Center, Karolinska Institutet, Stockholm, Sweden bDepartment of Neuroradiology, Karolinska University Hospital, Stockholm, Sweden cDepartment of Clinical Sciences, Karolinska Institutet, Stockholm, Sweden dDepartment of Rehabilitation Medicine, Danderyd Hospital, Stockholm, Sweden eDepartment of Health and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden fPain and Rehabilitation Centre, and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden gCentre for Person Centered Care (GPCC), University of Gothenburg, Gothenburg, Sweden hDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden iDepartment of Dental Medicine, Karolinska Institutet, Scandinavian Center for Orofacial Neurosciences (SCON), Huddinge, Sweden jDepartment of Molecular Medicine and Surgery, Karolinska Institutet, Center for Molecular Medicine (CMM), Karolinska University Hospital, Stockholm, Sweden kStockholm Spine Center, Lowenstromska Hospital, Upplands Vasby, Sweden.
• Pain. 2017 Jul 1; 158 (7): 1194-1203.

AbstractChronic 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.

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