Stress-induced bladder hypersensitivity: Effect of corticotropin releasing factor receptors assessed by spinal neurophysiology and neurochemistry. (15th February 2023)

• Record Type: Journal Article
• Authors: Robbins, Meredith T.; DeWitte, Cary; Ness, Timothy J.
• Is Part Of: Neuropharmacology. Volume 224(2023)
• Publication Date: 2023-02-15
• Subjects: Urinary bladder -- Chronic stress -- Pain hypersensitivity; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2022.109369
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Corticotropin releasing factor (CRF) receptors have been implicated in stress-induced hyperalgesia. The present study examined the role of CRF receptors Type 1&2 (CRFR1, CRFR2) in stress-induced bladder hyperalgesia in female rats by quantifying changes in receptor and agonist content following chronic (CFS, 7 daily episodes), acute (AFS, single episode) and control (NFS, no episodes) footshock protocols. ELISAs demonstrated that CFS lead to an increase in spinal thoracolumbar and lumbosacral spinal cord CRFR2 content and a decrease in lumbosacral spinal cord CRFR1 content. Content of the endogenous CRFR2 agonist, urocortin 2, was also increased in lumbosacral spinal cord and bladder tissues of CFS-pretreated rats, but urocortin 3 was decreased. Correlative single unit studies of lumbosacral dorsal horn neurons excited by bladder distension, in anesthetized rats that had undergone CFS, AFS or NFS protocols, used a before-after methodology with administration of a CRFR1 antagonist (antalarmin, 24 μg), CRFR2 antagonist (aSVG30, 12 μg) or normal saline topically to the exposed spinal cord following primary characterization. aSVG30 produced a reduction of neuronal responses evoked by bladder distension in CFS-pretreated rats but no statistically significant effects of aSVG30, antalarmin or vehicle were noted in other groups tested with the exception that antalarmin had an inhibitory effect on spontaneous activity in NFS-pretreated rats. The present findings are consistent with previous experiments using reflex responses to bladder distension as endpoints and further support a role for CRFR2-related mechanisms in stress-induced bladder hypersensitivity. This suggests CRFR2 antagonists may have efficacy in the treatment of bladder pain. Highlights: Corticotropin releasing factor receptors (CRFR1, CRFR2) & stress effects examined. Following chronic footshock lumbosacral spinal cord content of CRFR2 is increased. Following chronic footshock lumbosacral spinal cord content of CRFR1 is decreased. Following chronic footshock spinal cord content of CRFR2 agonist is increased.