The Double Insult of Neonatal Cystitis Plus Adult Somatic Inflammation Results in Corticotropin Releasing Factor Type II Receptor-Dependent Bladder Hypersensitivity in Female Rats.
Visceral pain
hypersensitivity
interstitial cystitis/bladder pain syndrome
somatic inflammation
Journal
The journal of pain
ISSN: 1528-8447
Titre abrégé: J Pain
Pays: United States
ID NLM: 100898657
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
received:
26
05
2022
revised:
23
08
2022
accepted:
26
08
2022
pubmed:
12
9
2022
medline:
10
12
2022
entrez:
11
9
2022
Statut:
ppublish
Résumé
The spinal mechanisms of visceral hypersensitivity are poorly understood, particularly when there is an interaction with somatic systems. Recently we demonstrated that rats which were pretreated with neonatal bladder inflammation (NBI) and subsequently pretreated as adults with bladder re-inflammation had augmented reflex and neuronal responses to urinary bladder distension via a corticotropin-releasing factor receptor type II (CRFR2) mechanism. Another insult producing similar augmented responses is somatic inflammation induced by Complete Freund's Adjuvant (CFA) in the hindlimb. Using neurochemical measures and both reflex and neuronal responses to urinary bladder distension as endpoints, the present study probed the role of CRFR2-related mechanisms in bladder hyperalgesia secondary to NBI and CFA-induced hindlimb inflammation. ELISA measures of the lumbosacral spinal cord demonstrated increased CRFR2 protein following pretreatment with NBI+CFA. Intrathecal CRFR2 antagonists blocked the augmentation of visceromotor responses to distension following pretreatment with both NBI+CFA. Lumbosacral dorsal horn neuronal responses to bladder distension in rats pretreated with NBI+CFA were attenuated by the spinal topical administration of a CRFR2 antagonist. These findings are the first demonstration of a somatovisceral interaction working via CRFR2 receptors and support the therapeutic value of these agents in the treatment of painful bladder disorders, particularly when triggered by somatic events. (Word Count 199). PERSPECTIVE: Bladder hypersensitivity occurs following neonatal cystitis and an adult insult such as somatic inflammation. This paper demonstrates that CRFR2-related mechanisms are associated with this hypersensitivity. This supports the therapeutic value of these agents in the treatment of painful bladder disorders, particularly when triggered by somatic events.
Identifiants
pubmed: 36089237
pii: S1526-5900(22)00388-1
doi: 10.1016/j.jpain.2022.08.005
pmc: PMC9729390
mid: NIHMS1835252
pii:
doi:
Substances chimiques
Corticotropin-Releasing Hormone
9015-71-8
Receptors, Corticotropin-Releasing Hormone
0
CRF receptor type 2
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2167-2178Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK051413
Pays : United States
Informations de copyright
Copyright © 2022 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.
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