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  • Innate immune response to bacterial urinary tract infection sensitises high-threshold bladder afferents and recruits silent nociceptors.

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    Author(s)
    Brierley, Stuart M
    Goh, Kelvin GK
    Sullivan, Matthew J
    Moore, Kate H
    Ulett, Glen C
    Grundy, Luke
    Griffith University Author(s)
    Ulett, Glen C.
    Sullivan, Matthew J.
    Goh, Kelvin
    Year published
    2019
    Metadata
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    Abstract
    The bladder is innervated by primary afferent nerve fibres that detect bladder distension and, through projections into the spinal cord, provide sensory input to the central nervous system circuits regulating bladder sensation and function. Uropathogenic E. coli (UPEC) bacteria are the primary cause of urinary tract infection (UTI) in adults, inducing clinical symptoms characterised by exaggerated bladder sensation, including urgency, frequency, and pelvic pain. However, the mechanisms underlying UTI-induced modulation of bladder afferent function are yet to be explored. Here, we isolated supernatants from the bladders of ...
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    The bladder is innervated by primary afferent nerve fibres that detect bladder distension and, through projections into the spinal cord, provide sensory input to the central nervous system circuits regulating bladder sensation and function. Uropathogenic E. coli (UPEC) bacteria are the primary cause of urinary tract infection (UTI) in adults, inducing clinical symptoms characterised by exaggerated bladder sensation, including urgency, frequency, and pelvic pain. However, the mechanisms underlying UTI-induced modulation of bladder afferent function are yet to be explored. Here, we isolated supernatants from the bladders of female mice acutely infected with UPEC (strain CFT073), or those sham-treated with phosphate buffered saline. Supernatants were then applied into the bladder lumen of healthy donor mice, and multiunit bladder afferent nerve responses to distension measured ex-vivo. Supernatant constituents from UPEC or sham-treated mice were analysed using a mouse cytokine multiplex assay. Supernatants from UPEC-infected mice significantly enhanced bladder afferent firing to distension in the absence of changes in muscle compliance. Further evaluation revealed that UPEC supernatants exclusively sensitised high-threshold bladder mechanoreceptors to graded bladder distension and also recruited a population of "silent nociceptors" to become mechanosensitive, thereby amplifying bladder afferent responses to physiological stimuli. UPEC supernatants contained significantly elevated concentrations of a range of cytokines released from innate immune cells, including but not limited to TNF-α, IL-1β, IL-6, IL-17, IFN-gamma, and MCP-1. These data provide novel mechanistic insight into how UPEC-mediated UTI induces bladder hypersensitivity and the symptoms of frequency, urgency, and pelvic pain.
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    Journal Title
    Pain
    DOI
    https://doi.org/10.1097/j.pain.0000000000001692
    Note
    This publication has been entered into Griffith Research Online as an Advanced Online Version
    Subject
    Biomedical and clinical sciences
    Clinical sciences
    Psychology
    Publication URI
    http://hdl.handle.net/10072/388768
    Collection
    • Journal articles

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