Experimentally Induced Bladder Permeability Evokes Bladder Afferent Hypersensitivity in the Absence of Inflammation

Frontiers in Neuroscience

卷:14

Luke Grundy¹  Ashlee Caldwell¹  Amanda Lumsden¹  Stuart M. Brierley¹  Gerhard Hannig³  Ehsan Mohammadi⁵  Beverley Greenwood Van-Meervald⁵ 

[1] Discipline of Medicine, University of Adelaide, North Terrace, Adelaide, SA, Australia;

[2] Hopwood Centre for Neurobiology, Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia;

[3] Ironwood Pharmaceuticals, Boston, MA, United States;

[4] Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK, United States;

[5] V.A. Medical Center, Oklahoma City, OK, United States;

[6] Visceral Pain Research Group, Flinders Health and Medical Research Institute (FHMRI), Flinders University, Bedford Park, SA, Australia;

关键词: bladder;    afferent;    interstitial cystitis;    bladder pain syndrome;    urothelium;    permeability;   

DOI  :  10.3389/fnins.2020.590871

来源: DOAJ

【 摘 要 】

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic urological condition characterised by urinary urgency, frequency and pelvic pain, that significantly impacts the quality of life for ∼5% of women. Bladder sensation is coordinated by primary afferent sensory neurons that innervate the bladder wall, translating bladder stretch into signals that travel to the brain via the spinal cord. Whilst the pathophysiology of IC/BPS remains unknown, an increase in the permeability of the bladder urothelium has been proposed as an initiating cause. Here we experimentally increased bladder permeability and tracked bladder afferent sensitivity for up to 28 days. We found that one day after increasing bladder epithelial permeability with in vivo bladder infusion of protamine sulfate, mechanosensitive bladder afferents exhibited significant hypersensitivity to bladder filling. This mechanical hypersensitivity was characterised by significantly increased peak afferent firing rates and a decrease in the activation threshold of individual afferents. Bladder afferent hypersensitivity occurred in the absence of inflammation and changes in bladder muscle compliance, indicating a direct sensitisation of peripheral afferent endings. Bladder afferent mechanosensitive responses to distension returned to control levels by day 7 post-protamine sulfate treatment and remained at control levels at 28-days post-treatment. Here we demonstrate, contrary to the prevailing hypothesis, that increased bladder permeability alone does not induce chronic bladder afferent sensitisation. Whilst experimentally induced changes in bladder permeability are able to induce transient bladder afferent hypersensitivity in the absence of inflammation, highly regulated homeostatic mechanisms exist to rapidly repair the urothelial barrier and normalise bladder afferent mechanosensitivity. Together, these data suggest that additional pathophysiology is required to induce chronic bladder dysfunction.

【 授权许可】

Unknown