Vestibulodynia presentation is differentiated by the presence of additional chronic primary pain conditions.

Vestibulodynia (VBD) is a common chronic primary pain condition (CPPC) defined by the presence of recurrent vulvovaginal pain with no obvious root cause. As many as 3 in 4 women with VBD may have co-occurring CPPCs, such as episodic migraine, fibromyalgia, irritable bowel syndrome, and temporomandibular disorder. The purpose of the present study was to compare pain and pain-related factors in women with VBD alone and those with VBD and co-occurring CPPCs (VBD+). We enrolled 45 women with VBD, 106 with VBD+, and 198 pain-free controls, who underwent a highly specific gynecological examination, quantitative sensory testing at remote body sites, and completed an extensive array of questionnaires assessing various physical and psychological experiences. Blood samples were also collected for genome-wide association study (GWAS). Results demonstrated that women with VBD+ had distinct patterns of heightened local vulvovaginal pain intensity and increased pain sensitivity at remote body site compared to those with VBD. Further women with VBD+ reported taking more medications indicated for pain and greater adverse mood states, somatic and psychological symptoms, and pain catastrophizing. Finally, case-control GWAS analysis identified distinct genetic variants associated with VBD and VBD+ subtypes. Variants associated with VBD were located in genes that regulate reproductive and nervous system development, while those associated with VBD+ were located in genes implicated in synaptic transmission and related CPPC pathophysiology. Together, these findings emphasize the critical need for accounting for CPPC status in VBD diagnostic, mechanistic, and therapeutic methodologies. Perspective This study identifies co-occurring chronic primary pain conditions as a differentiating factor in vestibulodynia presentation, highlighting the need for precise diagnostic criteria and personalized treatment approaches to address heightened symptom burden and complexity.