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IntroductionProvoked vestibulodynia (PVD) is a common type of dyspareunia among young women. The patho-physiology remains largely unclear. Women with PVD have general pain hypersensitivity and often report additional pain symptoms. Signs point towards PVD being a chronic pain disorder similar to other syndromes of longstanding pain, including a common comorbidity of anxiety and depression. Polymorphism in the serotonin receptor gene, 5HT-2A, has been associated with other chronic pain disorders such as fibromyalgia but has not been investigated in PVD patients. AimWe aimed to investigate a possible contribution of polymorphism in the 5HT-2A gene to the etiology of PVD as well as a potential influence on pain sensitivity. MethodsIn this case-control study 98 women with PVD and 103 healthy controls between 18 and 44 years and in the same menstrual cycle phase completed questionnaires and underwent quantitative sensory testing. Venous blood samples were collected for DNA isolation. Main Outcome MeasuresConcomitant pain was reported, a bodily pain score was created and pressure pain thresholds (PPTs) on the arm, leg, and in the vestibule were measured. Intensity of coital pain was rated on a visual analog scale, range 0-100. The T102C (rs6313) and A-1438G (rs6311) single nucleotide polymorphisms (SNPs) in the 5HT-2A gene were analyzed. ResultsThe probability of PVD was elevated in participants carrying the 1438G- and 102C-alleles of the 5HT-2A gene (OR 2.9). The G-/C- genotypes were also associated with more concomitant bodily pain in addition to the dyspareunia, but not with experimental PPTs or coital pain ratings. PVD patients reported more concomitant bodily pain and had lower PPTs compared with controls. ConclusionThe results indicate a contribution of alterations in the serotonergic system to the patho-genesis of PVD and gives further evidence of PVD being a general pain disorder similar to other chronic pain disorders. Heddini U, Bohm-Starke N, Gronbladh A, Nyberg F, Nilsson KW, and Johannesson U. Serotonin receptor gene (5HT-2A) polymorphism is associated with provoked vestibulodynia and comorbid symptoms of pain. J Sex Med 2014;11:3064-3071.