A familial aggregation of PVD has not yet been proven, however twin studies have shown a heritability of 13-50% in other longstanding, predominately female pain disorders, such as fibromyalgia, IBS and migraine. It is thought that a triggering insult is required for a chronic pain condition to develop, but there are also susceptibility factors that might be inherited.
Candidate gene association studies.
The assumed genetic predisposition for developing PVD has been investigated to some extent. There are scientific evidences of a neurogenic inflammation in the vestibular mucosa in PVD patients and they are more likely to be homozygous for allele 2 of the IL-1 receptor antagonist gene involved int the pro-inflammatory tissue response.
Recurrent vulvo-vaginal Candida infections have been reported as a trigger of PVD symptoms. A higher frequency of a variant of the gene coding for mannose-binding lectin, an innate immune antimicrobial protein that inhibits Candida proliferation, has been associated with PVD.
Also the influence of hormonal contraceptives as risk factor for developing PVD has been targeted genetically. Women carrying a variant androgen receptor gene, with longer CAG-repeats, might be at higher risk of developing PVD while using combined hormonal contraceptives then women carrying shorter alleles.
Some genes effecting endogenous pain modulation has been studied in this patient group. Both the opioid and serotonergic systems have wide-ranging actions throughout the body, not limited to pain modulation but also effects anxiety, stress response, sexual behavior and sexual function. The A118G SNP in the OPRM1 gene results in an altered μ-opioid receptor with a supposedly higher binding affinity of β-endorphin. The 118G-haplotype has been associated with pain protection, lower PPTs and less chronic pain. The 118A genotype of the the OPRM1 gene has been found to be more common in PVD patients than in controls.
The A-1438G and T102C SNPs in the 5HT-2A gene has been associated to an altered function of the serotonin receptor. This polymorphism has been associated to fibromyalgia, TMD and CWP. The TC/CC genotype of the 5HT-2A gene was more common in PVD patients than in controls, strengthening the notion of PVD being a disorder akin to these.
Differences in inflammatory response and immune defense might explain pain developing after candida infection.
Differences in androgen receptor function and GCH1-gene polymorphism might explain pain developing after use of hormonal contraceptives.
Differences in the opioid and the serotonergic systems might contribute to both pain hypersensitivity and psychosexual characteristics seen in this patient group.
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