Patients with urological chronic pelvic pain syndrome (UCPPS) experience chronic pelvic pain (CPP) and lower urinary tract symptoms (LUTS). The UCPPS symptoms are closely associated with nociceptive sensitization in the nervous system, which underlies visceral allodynia and hyperalgesia. Previous studies suggested that afferent hypersensitivity in bladder-projecting sensory neurons plays an important role in the generation and the maintenance of UCPPS symptoms, especially bladder pain and urinary frequency. As a glia biologist, I am interested in the neuromodulatory role of peripheral glial fibrillary acidic protein-expressing (GFAP+) glia in micturition and their therapeutic potential in benign bladder disorder. We have identified that satellite glial activation in lumbosacral sensory ganglia alleviates inflammatory pain in mice. In addition, terminal Schwann cell signaling also contribute to nerve injury-induced neuropathic pain. These data suggested the strong therapeutic potential of peripheral GFAP+ glial signaling in acute control of afferent excitability. Our findings suggest that Gq-GPCR activation in peripheral GFAP+ glia might be a promising and highly innovative approach to alleviate the symptoms of bladder overactivity and pain. The current work focuses on 1) developing experimental approaches for targeted activation of Gq-GPCR signaling pathways in sensory SGCs; 2) assessing the changes in lumbosacral bladder afferent sensitivity following glial Gq-GPCR activation; and 3) evaluating the glial activation-induced changes in LUTS and visceral hypersensitivity in vivo and in mouse models of UCPPS. Gq-coupled Designer Receptors Exclusively Activated by Designer Drugs (Gq-DREADD) is used to selectively activate Gq-GPCR signaling cascades in lumbosacral sensory SGCs via targeted adeno-associated virus (AAV) delivery. Afferent sensitivity and bladder functions are evaluated in vivo by well-established and clinically relevant visceral nociceptive assays and urodynamic assays. This project aims to characterize the role of SGC Gq-GPCR signaling in regulating visceral nociception in vivo as well as test its therapeutic potential to reverse pain and voiding dysfunction in UCPPS patients. The Xie lab works in close collaboration with other research labs in the Basic and Translational Urology Research Program in the Division of Urology, Department of Surgery.