title: Differential effects of intravesical resiniferatoxin on excitability of bladder spinal neurons upon colon-bladder cross-sensitization.
abstract: Cross-sensitization in the pelvis may contribute to etiology of functional pelvic pain disorders such as interstitial cystitis/bladder pain syndrome (IC/BPS). Increasing evidence suggests the involvement of transient receptor potential vanilloid 1 (TRPV1) receptors in the development of neurogenic inflammation in the pelvis and pelvic organ cross-sensitization. The objective of this study was to test the hypothesis that desensitization of TRPV1 receptors in the urinary bladder can minimize the effects of cross-sensitization induced by experimental colitis on excitability of bladder spinal neurons. Extracellular activity of bladder neurons was recorded in response to graded urinary bladder distension (UBD) in rats pretreated with intravesical resiniferatoxin (RTX, 10(-7)M). Colonic inflammation was induced by intracolonic instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS). The duration of excitatory responses to noxious UBD during acute colonic inflammation (3 days post-TNBS) was significantly shortened in the group with RTX pretreatment (25.3±1.5s, n=49) when compared to the control group (35.1±4.2s, n=43, p<0.05). The duration of long-lasting excitatory responses, but not short-lasting responses of bladder spinal neurons during acute colitis was significantly reduced by RTX from 52.9±6.6s (n=21, vehicle group) to 34.4±2.1s (RTX group, n=21, p<0.05). However, activation of TRPV1 receptors in the urinary bladder prior to acute colitis increased the number of bladder neurons receiving input from large somatic fields from 22.7% to 58.2% (p<0.01). The results of our study provide evidence that intravesical RTX reduces the effects of viscerovisceral cross-talk induced by colonic inflammation on bladder spinal neurons. However, RTX enhances the responses of bladder neurons to somatic stimulation, thereby limiting its therapeutic potential.
authors.affiliation: Division of Urology, Department of Surgery, University of Pennsylvania School of Medicine, 500 S. Ridgeway Ave #158, Glenolden, PA, USA. anna.malykhina@uphs.upenn.edu
authors.forename: Anna P
authors.initials: AP
authors.lastname: Malykhina
authors.forename: Chao
authors.initials: C
authors.lastname: Qin
authors.forename: Qi
authors.initials: Q
authors.lastname: Lei
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Pan
authors.forename: Beverley
authors.initials: B
authors.lastname: Greenwood-Van Meerveld
authors.forename: Robert D
authors.initials: RD
authors.lastname: Foreman
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003092:Colitis / Q000503:physiopathology; D003106:Colon / Q000187:drug effects / Q000294:innervation*; D003627:Data Interpretation, Statistical; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D008160:Lumbosacral Plexus / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009475:Neurons, Afferent / Q000502:physiology; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000187:drug effects; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation*; D001745:Urinary Bladder Diseases / Q000503:physiopathology
chemical_list: D004224:Diterpenes; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D014302:Trinitrobenzenesulfonic Acid; C024353:resiniferatoxin