Chronic chemogenetic inhibition of TRPV1 bladder afferent promotes micturition recovery post SCI

Spinal cord injury often results in chronic loss of micturition control, which is featured by bladder hyperreflexia and detrusor sphincter dyssynergia. Previous studies showed that treatment of capsaicin reduces non-voiding bladder contractions in multiple animal injury models and human patients. However, its underlying neural mechanisms remain largely unknown. Here, by injecting a RetroAAV into the bladder wall, we specifically targeted TRPV1⁺, a capsaicin receptor, bladder afferent neurons. Morphometric analysis revealed borderline increase of the soma size and significant spinal axon sprouting of TRPV1⁺ bladder afferent neurons post a complete T8 spinal cord crush. We further demonstrated that chronic chemogenetic inhibition of these DRG neurons improved micturition recovery after SCI by increasing voiding efficiency and alleviating bladder hyperreflexia, along with reduced morphological changes caused by injury. Our study provided novel insights into the structural and functional changes of TRPV1⁺ bladder afferent post SCI and further supports the clinical use of capsaicin as an effective treatment to improve bladder functions in patients with SCI.