Abstract
The most common subtype of vulvodynia (idiopathic chronic vulvar pain) is provoked vestibulodynia (PVD). Previous imaging studies have shown that women with vulvodynia exhibit increased neural activity in pain-related brain regions (e.g., the secondary somatosensory cortex, insula, dorsal midcingulate, posterior cingulate, and thalamus). However, despite the recognized role of the spinal cord/brainstem in pain modulation, no previous neuroimaging studies of vulvodynia have examined the spinal cord/brainstem. Sixteen women with PVD and sixteen matched Control women underwent a spinal cord/brainstem functional magnetic resonance imaging (fMRI) session consisting of five runs with no painful thermal stimuli (No Pain), interleaved randomly with five runs with calibrated, moderately painful heat stimulation (Pain). Functional connectivity was also assessed in periods before, during, and after, pain stimulation to investigate dynamic variations in pain processing throughout the stimulation paradigm. Functional connectivity in the brainstem and spinal cord for each group was examined using structural equation modeling (SEM) for both Pain and No Pain conditions. Significant connectivity differences during stimulation were identified between PVD and Control groups within pain modulatory regions. Comparisons of Pain and No Pain conditions identified a larger number of connections in the Control group than in the PVD group, both before and during stimulation. The results suggest that women with PVD exhibit altered pain processing and indicate an insufficient response of the pain modulation system. This study is the first to examine the spinal cord/brainstem functional connectivity in women with PVD, and it demonstrates altered connectivity related to pain modulation in the spinal cord/brainstem.
Highlights
Provoked Vestibulodynia (PVD) is characterized by pain evoked by pressure to the vaginal entrance and is the most common subtype of vulvodynia [1]
There was a main effect of study condition (Pain vs. no painful thermal stimuli (No painful heat stimulation (Pain))) in connectivity from the locus coeruleus (LC) and parabrachial nucleus (PBN) to the spinal cord, and from the hypothalamus to the periaqueductal gray matter (PAG)
A key feature of our results is that women with provoked vestibulodynia (PVD) were observed to have similar connectivity values between regions of the BS/SC known to play a role in pain perception regardless of whether or not a noxious heat stimulus was applied to their hand, suggesting they consistently exhibited altered pain processing on a neurophysiological level, in contrast to Control participants without chronic pain
Summary
Provoked Vestibulodynia (PVD) is characterized by pain evoked by pressure to the vaginal entrance and is the most common subtype of vulvodynia (i.e., idiopathic chronic vulvar pain) [1]. The possibility that central pain processing in the brain and spinal cord is modified in this condition has prompted a number of investigations into neuroanatomical and functional differences in women with vulvodynia (mostly PVD) These studies have provided evidence of altered pain processes in the form of greater gray matter density and altered microstructural organization in brain regions [8,9,10], augmented brain activity in pain processing regions in response to vulvar [11, 12] and thumb pressure [13], and alterations of sensorimotor, salience, and default mode network intrinsic connectivity [14]. We hypothesize that women with PVD will exhibit altered connectivity in regions known to be related to pain processing in the BS/SC cord, indicating diminished descending modulation
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