A118G polymorphism in the μ-opioid receptor gene and levels of β-endorphin are associated with provoked vestibulodynia and pressure pain sensitivity

• Background and aimsProvoked vestibulodynia (PVD) is the most common cause of dyspareunia among young women. The aetiology is largely unknown and treatment is often extensive and longstanding with varying outcomes. Patients display general pain hypersensitivity and there are correlations with other chronic pain syndromes such as fibromyalgia later in life. The A118G polymorphism in the μ-opioid receptor (OPRM1) gene influences endogenous pain regulation and pain sensitivity, but has not been studied in this patient group before. We aimed to investigate a possible association between A118G polymorphism and PVD, with correlation to plasma levels of β-endorphin, and to explore relationships between this polymorphism and pain sensitivity among women with PVD and healthy controls.MethodsThis case–control study included 98 women with PVD and 103 controls. Participants filled out study-specific questionnaires and underwent quantitative sensory testing of pressure pain thresholds on the arm, leg and in the vestibular area. Levels of β-endorphin were analyzed by radioimmunoassay using the EURIA-beta-endorphin kit, and the A118G single-nucleotide polymorphism (SNP; rs1799971) in the OPRM1 gene was analyzed using the TaqMan SNP genotyping assay.ResultsThe 118G allele was more common in controls (44%) than in patients (30%) (p  = 0.042). The odds ratio of having PVD was 1.8 in participants carrying the 118A allele compared to participants hetero- or homozygous for the 118G allele (OR = 1.846, CI: 1.03–3.31, p = 0.039). Pressure pain thresholds on the leg were higher for participants carrying the 118G allele (mean 480 kPa, SD 167.5) than for those carrying the 118A allele (mean 419, SD 150.4, p = 0.008). Levels of β-endorphin were higher in patients (mean 17.9 fmol/ml, SD 4.71) than in controls (mean 15.8 fmol/ml, SD 4.03) (p < 0.001).ConclusionWe found an association between the A118G polymorphism in the OPRM1 gene and an increased risk of PVD and increased pain sensitivity among participants carrying the 118A allele. PVD patients were more sensitive to pressure pain and had higher levels of plasma β-endorphin than controls. The results indicate that differences in endogenous pain modulation involving the opioid system could contribute to the pathophysiology of PVD and the general pain hypersensitivity seen in these women.ImplicationsThe data support the conceptualization of PVD as part of a general pain disorder with a possible genetic predisposition. The age of onset of PVD is usually between 18 and 25 years and already at this age general pain hypersensitivity is present but rarely causing disability. We believe that early recognition and treatment, with the risk of further development of chronic pain taken into consideration, might prevent future aggravated pain problems in this patient group.

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MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

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