title: Acute colonic inflammation triggers detrusor instability via activation of TRPV1 receptors in a rat model of pelvic organ cross-sensitization.
abstract: Chronic pelvic pain of unknown etiology is a common clinical condition and may develop as a result of cross-sensitization in the pelvis when pathological changes in one of the pelvic organs result in functional alterations in an adjacent structure. The aim of the current study was to compare transient receptor potential vanilloid 1 (TRPV1) activated pathways on detrusor contractility in vivo and in vitro using a rat model of pelvic organ cross-sensitization. Four groups of male Sprague-Dawley rats (N = 56) were included in the study. Animals received intracolonic saline (control), resiniferatoxin (RTX, TRPV1 agonist, 10(-7) M), 2,4,6-trinitrobenzene sulfonic acid (TNBS, colonic irritant), or double treatment (RTX followed by TNBS). Detrusor muscle contractility was assessed under in vitro and in vivo conditions. Intracolonic RTX increased the contractility of the isolated detrusor in response to electric field stimulation (EFS) by twofold (P ≤ 0.001) and enhanced the contractile response of the bladder smooth muscle to carbachol (CCh). Acute colonic inflammation reduced detrusor contractility upon application of CCh in vitro, decreased bladder capacity by 28.1% (P ≤ 0.001), and reduced micturition volume by 60% (P ≤ 0.001). These changes were accompanied by an increased number of nonmicturition contractions from 3.7 ± 0.7 to 15 ± 2.7 (N = 6 in both groups, P ≤ 0.001 vs. control). Desensitization of intracolonic TRPV1 receptors before the induction of acute colitis restored the response of isolated detrusor strips to CCh but not to EFS stimulation. Cystometric parameters were significantly improved in animals with double treatment and approximated the control values. Our data suggest that acute colonic inflammation triggers the occurrence of detrusor instability via activation of TRPV1-related pathways. Comparison of the results obtained under in vitro vs. in vivo conditions provides evidence that intact neural pathways are critical for the development of an overactive bladder resulting from pelvic organ cross talk.
authors.affiliation: Division of Urogynecology and Pelvic Reconstructive Surgery, Department of Obstetrics and Gynecology, University of Pennsylvania, Glenolden, Pennsylvania 19036-2307, USA.
authors.forename: Tirsit S
authors.initials: TS
authors.lastname: Asfaw
authors.forename: Joseph
authors.initials: J
authors.lastname: Hypolite
authors.forename: Gina M
authors.initials: GM
authors.lastname: Northington
authors.forename: Lily A
authors.initials: LA
authors.lastname: Arya
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Wein
authors.forename: Anna P
authors.initials: AP
authors.lastname: Malykhina
mesh_terms: D000208:Acute Disease; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018678:Cholinergic Agents / Q000494:pharmacology; D003092:Colitis / Q000139:chemically induced / Q000150:complications* / Q000503:physiopathology*; D004224:Diterpenes / Q000494:pharmacology; D004558:Electric Stimulation; D008297:Male; D023421:Models, Animal; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D017699:Pelvic Pain / Q000209:etiology* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D050916:TRPV Cation Channels / Q000187:drug effects / Q000502:physiology*; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000209:etiology* / Q000503:physiopathology*
chemical_list: D018678:Cholinergic Agents; D004224:Diterpenes; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D014302:Trinitrobenzenesulfonic Acid; D002217:Carbachol; C024353:resiniferatoxin