title: Lack of TRPV1 inhibits cystitis-induced increased mechanical sensitivity in mice.
abstract: Transient receptor potential vanilloid 1 (TRPV1) is highly expressed in primary afferent neurons. Tissue damage generates an array of chemical mediators that activate and sensitize afferent nerve fibers, and sensitization of afferent nerve fibers plays an important role in development of visceral pain. We investigated participation of TRPV1 in visceral pain associated with bladder inflammation induced in mice by systemic treatment with cyclophosphamide or intravesical instillation of acrolein. The effects of experimental cystitis on bladder function (an indicator of visceral pain) and the threshold of response to mechanical or thermal stimuli of the hind paws were investigated using TRPV1 knock-out (KO) and congenic wild-type (WT) mice. We found that cystitis induced bladder mechanical hyperreactivity and increased mechanical sensitivity of hind paws in WT, but not in TRPV1 KO mice. Lack of functional TRPV1 did not inhibit development of histological evidence of bladder inflammation, or increased expression of mRNAs for nerve growth factor, endothelial nitric oxide synthase, cyclooxygenase-2 and bradykinin receptors in urothelium. Cystitis did not affect the threshold of response to thermal stimuli in WT or KO mice. These results suggest that TRPV1 is essential for cystitis-induced bladder mechanical hyperreactivity. Also, TRPV1 participates in development of visceral pain, as reflected by referred increased mechanosensitivity in peripheral tissues in the presence of visceral inflammation.
authors.affiliation: Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 2015 Linden Drive, Madison, WI 53719, USA.
authors.forename: Zun-Yi
authors.initials: ZY
authors.lastname: Wang
authors.forename: Peiqing
authors.initials: P
authors.lastname: Wang
authors.forename: Fabiola Voznika
authors.initials: FV
authors.lastname: Merriam
authors.forename: Dale E
authors.initials: DE
authors.lastname: Bjorling
mesh_terms: D000818:Animals; D003556:Cystitis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010146:Pain / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010812:Physical Stimulation / Q000379:methods; D050916:TRPV Cation Channels / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D001743:Urinary Bladder / Q000473:pathology / Q000502:physiology
chemical_list: D018836:Inflammation Mediators; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse