Spinal neuronal activity and neuroinflammatory component in a mouse model of CFA-induced vestibulodynia

: Vestibulodynia is a complex pain disorder characterized by chronic discomfort in the vulvar region, often accompanied by tactile allodynia and spontaneous pain. In patients a depressive behaviour is also observed. In this study, we have used a model of vestibulodynia induced by complete Freund's adjuvant (CFA) focusing our investigation on the spinal cord neurons and microglia. We investigated tactile allodynia, spontaneous pain, and depressive-like behavior as key behavioral markers of vestibulodynia. In addition, we conducted in vivo electrophysiological recordings to provide, for the first time to our knowledge, the characterization of the spinal sacral neuronal activity in the L6-S1 dorsal horn of the spinal cord. Furthermore, we examined microglia activation in the L6-S1 dorsal horn using immunofluorescence, unveiling hypertrophic phenotypes indicative of neuroinflammation in the spinal cord. This represents a novel insight into the role of microglia in vestibulodynia pathology. To address the therapeutic aspect, we employed pharmacological interventions using GABApentin, amitriptyline, and PeaPol. Remarkably, all three drugs, also used in clinic, showed efficacy in alleviating tactile allodynia and depressive-like behavior. Concurrently, we also observed a normalization of the altered neuronal firing and a reduction of microglia hypertrophic phenotypes. In conclusion, our study provides a comprehensive understanding of the CFA-induced model of vestibulodynia, encompassing behavioral, neurophysiological and neuroinflammatory aspects. These data pave the way to investigate spinal cord first pain plasticity in vestibulodynia.