Author: Harman Sharma
Sharma, Harman, 2025 Role of bladder sensory neurons in urinary tract infection and chronic bladder hypersensitivity, Flinders University, College of Medicine and Public Health
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The bladder is a complex organ, finely regulated by an intricate network of sensory and autonomic nerves that work together to maintain homeostasis. Sensory nerves are responsible for detecting bladder fullness and transmitting signals of pain or discomfort to the spinal cord and brain. These nerves respond to various stimuli, including the stretching of the bladder or chemical signals within the bladder environment. Meanwhile, autonomic nerves control the contraction and relaxation of the bladder muscles, ensuring efficient storage and timely voiding of urine. Any disruption in this delicate balance can lead to significant alterations in bladder sensation and function, resulting in a variety of bladder disorders, including chronic pain or overactive bladder conditions.
This thesis explored the mechanisms that regulate bladder sensation and function, with a particular focus on how these processes are altered in both normal and pathological states, such as urinary tract infections (UTIs). UTIs are a widespread health issue that can lead to lasting impairments in bladder function, largely through their effects on the bladder’s sensory innervation. Despite the prevalence of UTIs, there is a critical knowledge gap regarding how these infections can induce long-term changes in sensory pathways, contributing to chronic bladder dysfunction. Current treatments for these conditions typically focus on managing symptoms rather than addressing the underlying neural alterations that drive persistent bladder pain and dysfunction. This research seeks to fill this gap by investigating how acute UTI, induced by uropathogenic Escherichia coli (UPEC), may cause enduring changes in bladder sensory nerves, persisting well beyond the initial infection period.
First, we examined the location and characteristics of bladder afferent and efferent nerve endings, identifying distinct nerve populations using specific markers. While we found no direct interaction between these nerves, their close proximity suggests the potential for indirect communication, which may play a role in altering bladder function after infection. To explore this further, we developed a mouse model of uropathogenic Escherichia coli (UPEC)-induced UTI to investigate its impact on bladder afferent nerve sensitivity. The findings show that acute UTI significantly increases nerve sensitivity and alters bladder function, likely driven by infection-induced inflammation, establishing a crucial link between immune response and disrupted sensory signalling in the bladder. Finally, we investigated the long-term effects of a single UTI on bladder sensory pathways. Our results revealed that persistent changes in nerve function, along with ongoing alterations in gene expression related to immune activation and neuronal processes, remain long after the initial infection. These findings suggest that the altered sensory innervation during a UTI not only drives acute symptoms but may also predispose individuals to chronic conditions such as ongoing pain and bladder dysfunction.
By addressing the knowledge gap around how UTIs disrupt bladder sensory pathways, this thesis provides new insights into the neural mechanisms underlying acute and chronic bladder conditions. It underscores the need for treatment approaches that target the root causes of nerve dysfunction, rather than just managing symptoms, paving the way for more effective therapies to reduce chronic bladder pain and dysfunction.
Keywords: Afferent, Bladder, Cystitis, Lower urinary tract symptoms, Urinary tract infection, Uropathogenic E. coli., Sensory, Chronic inflammation, Hypersensitivity
Subject: Medicine thesis
Thesis type: Doctor of Philosophy
Completed: 2025
School: College of Medicine and Public Health
Supervisor: Luke Grundy