Provoked vestibulodynia : studies on pain genetics and pain co-morbidity
Objective: The purpose of this thesis was to investigate a possible genetic predisposition for developing provoked vestibulodynia (PVD), focusing on previously defined single nucleotide polymorphisms (SNPs) in three genes with a known influence on endogenous pain modulation: GCH1, OPRM1 and 5HT-2A. We also investigated the effects of any potential interactions between these SNPs and the use of hormonal contraceptives, serum levels of β-endorphin and symptoms of anxiety and depression, on the risk of developing PVD and general pain sensitivity. Potential predictors of treatment outcome and the prevalence of pain co-morbidity among women with PVD were also explored.
Materials and methods: The thesis is based on one descriptive study and three case-control studies which included 109 women with PVD and 103 healthy controls who underwent quantitative sensory testing and filled out study-specific questionnaires. Venous blood samples were collected for genetic analyses and β-endorphin quantification.
Results: The results showed that the probability of being diagnosed with PVD was elevated in carriers of the 118A genotype (rs1799971) of the OPRM1 gene (OR 1.8) and the 102C genotype (rs6313 ) of the 5HT-2A gene (OR 2.9) but not in carriers of the studied SNPs in the GCH1 gene (rs8007267, rs3783641 and rs10483639). However, there appeared to be an interactive effect between the GCH1 SNPs and use of hormonal contraceptives, with respect to pain sensitivity among women who were currently receiving treatment for PVD. There was increased pressure pain sensitivity among participants carrying the 118A genotype of the OPRM1 gene and those with PVD were more sensitive than healthy controls to pressure pain and had higher levels of plasma β-endorphin. The probability for PVD was also elevated among participants with symptoms of anxiety (OR 5.2). Higher prevalence of concomitant bodily pain was correlated with the 102C genotype of the 5HT-2A gene and with anxiety. A successful treatment outcome was more likely in women with PVD who had fewer other concomitant pain conditions and in those with secondary PVD. The number of other bodily pain conditions was also associated with the intensity of coital pain.
Conclusions: The results of these studies indicate that specific genetic polymorphisms in the opioid and serotonin systems that affect endogenous pain modulation contribute to the risk of developing PVD. This substantiates the findings of earlier studies, which found greater general pain sensitivity and more anxiety symptoms in patients than in controls. Women with PVD who had more pronounced general pain dysfunction and those who had primary PVD were less likely to achieve a satisfactory treatment outcome. These findings strengthen the concept that PVD is a general pain condition.
Clinical implications: It is proposed that a careful medical history be carried out in women with PVD to investigate the degree of concomitant pain disorders and to establish the subgroup of PVD so as to identify patients who could benefit from referral to specialist centers. Early recognition and treatment of the disorder could, in addition to restoring the sexual health of the affected women, also prevent aggravated chronic pain problems in this patient group.
List of scientific papers
I. Ulrika Heddini, Nina Bohm-Starke, Kent W. Nilsson, and Ulrika Johannesson. Provoked Vestibulodynia - medical factors and comorbidity associated to treatment outcome. J Sex Med. 2012;9:1400–1406.
https://doi.org/10.1111/j.1743-6109.2012.02665.x
II. Ulrika Heddini, Nina Bohm-Starke, Alfhild Grönbladh, Fred Nyberg, Kent W. Nilsson, Ulrika Johannesson. GCH1-polymorphism and pain sensitivity among women with provoked vestibulodynia. Mol Pain. 2012; 12:8:68.
https://doi.org/10.1186/1744-8069-8-68
III. Ulrika Heddini, Ulrika Johannesson, Alfhild Grönbladh, Fred Nyberg, Kent W. Nilsson, Nina Bohm-Starke. A118G polymorphism in the μ-opioid receptor gene and levels of β-endorphin are associated with provoked vestibulodynia and pressure pain sensitivity. Scan J of Pain. 2013.
https://doi.org/10.1016/j.sjpain.2013.10.004.
IV. Ulrika Heddini, Nina Bohm-Starke, Alfhild Grönbladh, Fred Nyberg, Kent W. Nilsson, Ulrika Johannesson. Serotonin receptor gene (5HT-2A) polymorphism and anxiety are associated to provoked vestibulodynia and co-morbid symptoms of pain. [Submitted]
History
Defence date
2014-02-07Department
- Department of Clinical Sciences, Danderyd Hospital
Publisher/Institution
Karolinska InstitutetMain supervisor
Bohm-Starke, NinaPublication year
2014Thesis type
- Doctoral thesis
ISBN
978-91-7549-357-2Number of supporting papers
4Language
- eng