Acute urinary tract infection elicits bladder afferent hypersensitivity

Urinary tract infections (UTIs) are one of the most common bacterial infections globally, with over 400 million cases annually (Yang et al., 2022). Acute UTI can trigger a variety of distinctive bladder sensations, including dysuria, urinary urgency, irritation, and pelvic pain that disrupt the normal rhythm of periodic micturition and provoke rapid and frequent bladder voiding (Yang et al., 2022; Hooton, 2012). Despite this, the neurophysiology underlying aberrant bladder sensation and altered bladder function during UTI have yet to be determined.

Bladder sensations originate in the periphery, via the activation of sensory (afferent) nerves embedded throughout the bladder wall (Grundy et al.). Mechanosensory bladder afferents are activated during bladder distension and sensory signals feed into central nervous system (CNS) pathways that initiate bladder sensations and ultimately regulate bladder function (de Groat and Yoshimura, 2009; Fowler et al., 2008). During inflammation, pro-inflammatory mediators can disrupt normal bladder afferent function, causing them to become hypersensitive, a process known as peripheral sensitisation, that underpins the development of pain (de Groat and Yoshimura, 2009; Grundy et al., 2018a; Hucho and Levine, 2007; Wyndaele et al., 2024). Referred pelvic pain is a key feature of UTI in animal models (Montalbetti et al., 2022; Rosen and Klumpp, 2014) and hyperexcitability of bladder afferent pathways is a crucial mechanism underlying the development of the exaggerated sensations that define multiple inflammatory bladder disorders (Grundy et al.; de Groat and Yoshimura, 2009; Fowler et al., 2008; Grundy et al., 2018a; Wyndaele et al., 2024; Montalbetti et al., 2022). However, whether bladder afferent hypersensitivity to bladder distension develops during UTI has yet to be determined.

The aim of this study was to characterise the impact of UTI on bladder afferent signalling and bladder function using a preclinical model. We report that UTI induces hypersensitivity of low-threshold mechanosensitive afferents during bladder distension and the development of altered voiding patterns indicative of bladder dysfunction.