Author: Cindy Tay
Tay, Cindy, 2025 Determining the contribution of muscular and mucosal afferents to bladder sensory signalling in health and disease, Flinders University, College of Medicine and Public Health
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The bladder is a vital organ responsible for the storage and excretion of urine, a process governed by intricate sensory signalling pathways connecting the bladder, spinal cord, and brain. Sensory pelvic afferents relay critical information about bladder fullness and discomfort, activating neural circuits to initiate voiding. Disruptions in this finely tuned system lead to lower urinary tract symptoms (LUTS), characterised by increased urinary frequency, urgency, pelvic pain, and dysuria. These debilitating symptoms are prevalent across a range of bladder pathologies, including interstitial cystitis/bladder pain syndrome (IC/BPS), overactive bladder (OAB), neurogenic bladder, and urinary tract infections (UTIs). Unlike the normal spectrum of bladder sensations, these conditions reflect altered sensory processing, prompting the need to elucidate the underlying mechanisms and identify specific nerve subpopulations driving these abnormal sensations.
This research delineates two key populations of bladder-innervating nerves: muscular afferents, responsible for sensing stretch during bladder filling, and stretch-insensitive mucosal afferents, whose physiological role has remained elusive. Detailed analysis revealed a dense network of mucosal nerve endings extending into the urothelial cell layer, the primary site of bladder inflammation and infection. To investigate the function of mucosal afferents, a novel mouse model of selective bladder mucosal afferent denervation was developed. This model enabled the precise removal of mucosal afferents, both anatomically and functionally, and demonstrated that these afferents are not required for normal bladder voiding.
Further exploration, using this model in conjunction with an acute UTI model, revealed that mucosal afferents are key mediators of bladder pathology. These afferents were shown to become hyperactive during UTI, induce pelvic pain, and play a potential role in bacterial clearance and immune regulation during infection. This study highlights mucosal afferents as pivotal players in the bladder’s response to pathological states.
By uncovering the physiological and pathological roles of bladder mucosal afferents, this thesis provides transformative insights into the mechanisms of sensory nerve function in the bladder. These findings lay the foundation for the development of innovative therapeutic strategies to alleviate LUTS and improve quality of life for individuals suffering from bladder dysfunctions.
Keywords: Bladder innervation, Mucosal afferents, Urinary tract infection, Neuroimmune interactions
Subject: Medicine thesis
Thesis type: Doctor of Philosophy
Completed: 2025
School: College of Medicine and Public Health
Supervisor: Dr Luke Grundy