A Translational Investigation of the Effect of Genital and Tibial Neuromodulation on Gynecological Hemodynamics
Bottorff, Elizabeth
2023
Abstract
Sexual function is intricately tied to life satisfaction and has an important role in social, emotional, and mental well-being. An estimated 22-43% of women have poor sexual function, and people with spinal cord injury (SCI) also report it as a high priority to restore. Existing treatment options are limited, particularly for the broad range of gynecological dysfunctions. Neuromodulation has the potential to treat sexual dysfunction by providing a targeted therapy that taps into existing neural circuits. Pudendal nerve and tibial nerve neuromodulation have demonstrated potential as a treatment in preclinical and clinical studies, but more needs to be understood about their mechanisms for improving female sexual dysfunction (FSD) symptoms. In this dissertation, I performed translational studies examining physiological responses to neuromodulation in rodent and human subjects under different paradigms that yielded insights into its potential as a therapy for sexual dysfunction. The first Aim of my dissertation was to investigate the effect of pudendal and tibial nerve stimulation on genital blood flow in anesthetized rats. Vulvar blood perfusion was recorded with a laser speckle contrast imager during baseline, nerve stimulation, and recovery periods. I found that pudendal, but not tibial, nerve stimulation can increase vulvar blood perfusion during stimulation. These results suggest that pudendal stimulation can drive short-term responses and that rodent vulvar blood perfusion needs further investigation to determine its potential as a preclinical sexual function biomarker. In the second Aim of this dissertation, we measured genital blood flow with vaginal photoplethysmography (VPG) during baseline, stimulation, and recovery periods for genital (distal pudendal nerve) and tibial nerve stimulation (GNS/TNS). We recruited three cohorts of participants in a randomized crossover study design: women with SCI, participants with FSD, and non-dysfunction, healthy controls. We observed variable changes in genital arousal across participants and found that GNS but not TNS can increase subjective arousal, including in SCI participants. I hypothesize that differences between animal and human anatomy and cortical arousal states were contributing factors to the dissimilarity in genital arousal responses between the first two Aims. These factors are important to consider in future translational studies. A primary reason I believe the physiological data for Aim 2 were inconclusive was due to descending cortical inhibition and a lack of sexual stimuli in the study protocol. This observation led to my third dissertation Aim, in which we investigated the effect of GNS and TNS on the VPG response to erotic stimuli in the same cohorts as Aim 2. Participants viewed a sequence of neutral and erotic videos without and with nerve stimulation. We found low sexual concordance between VPG and subjective arousal and no conclusive trends in physiological genital arousal across all three groups. As in Aim 2, SCI and FSD participants expressed willingness to continue using neuromodulation. This study reaffirms the need to identify better biomarkers for sexual function that correlate with the sexual experience of people with gynecological anatomy. This dissertation examined neural control over gynecological arousal responses in rodent and human subjects and identified key areas of improvement for translational research in female sexual medicine. Although physiological responses varied within and across these studies, SCI and FSD study participants consistently expressed an interest in neuromodulation as a treatment for a condition that significantly affects their lives. This research further underscores the impact of FSD and the need for improved treatments.Deep Blue DOI
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peripheral neuromodulation for female sexual dysfunction
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