1002 ACUTE INFLAMMATION IN THE PELVIS MODULATES THE EXCITABILITY OF BLADDER EXTRINSIC SENSORY NEURONS VIA ACTIVATION OF VOLTAGE GATED SODIUM CHANNELS AND NON-SELECTIVE CATION CHANNELS

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Neurogenic Voiding Dysfunction1 Apr 20101002 ACUTE INFLAMMATION IN THE PELVIS MODULATES THE EXCITABILITY OF BLADDER EXTRINSIC SENSORY NEURONS VIA ACTIVATION OF VOLTAGE GATED SODIUM CHANNELS AND NON-SELECTIVE CATION CHANNELS Qi Lei, Xiao-Qing Pan, Alan Wein, and Anna Malykhina Qi LeiQi Lei More articles by this author , Xiao-Qing PanXiao-Qing Pan More articles by this author , Alan WeinAlan Wein More articles by this author , and Anna MalykhinaAnna Malykhina More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2016AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Chronic pelvic pain is a symptom of many functional pelvic disorders and develops as a result of cross-sensitization in the pelvis. Our recent studies demonstrated increased excitability of convergent dorsal root ganglion neurons receiving input from the distal colon and urinary bladder. The objective of this study was to clarify the mechanisms modulating the expression of voltage gated sodium (Na+) channels in bladder sensory neurons after acute inflammation in the pelvis. METHODS Sprague-Dawley male rats underwent survival surgeries for retrograde labeling of sensory neurons using Fast Blue (1.5 % w/v in water, 20-22 μl). Na+ channels were recorded in lumbosacral (L6-S2) dorsal root ganglia (DRG) neurons isolated from 4 groups of animals: control, resiniferatoxin (RTX) instillation in the colon, trinitrobenzene sulfonic acid (TNBS) induced experimental colitis and double treatment (RTX+TNBS). Animals were sacrificed 3 days after the last treatment. RESULTS Acute colonic inflammation increased the peak amplitude of total Na+ current in bladder DRG neurons by 2-fold at -30 mV (-102.7±41.0 pA/pF in control group vs -229.3±18.1 pA/pF in experimental group, p≤0.05). Activation of TRPV1 receptors in the colon had similar effects on the amplitude of total Na+ current in bladder neurons as in the colitis group. However, colonic application of RTX followed by TNBS-induced colitis significantly enhanced Na+ current in bladder DRG neurons from -102.7±41.0 pA/pF to – 364.6±60.1 pA/pF (n=12, p≤0.05). Acute colitis did not change voltage dependence of steady-state activation nor inactivation in bladder sensory neurons. However, these parameters were affected by RTX treatment. Thus, V1/2 of activation curve of total Na+ current after RTX application had a leftward shift from -27.80±4.78 mV in the control group to -42.20±1.75 mV in RTX group (n=10, p≤0.05) whereas inactivation curve was shifted from -37.75±3.64 mV to -42.94±5.80 mV. Pretreatment with RTX followed by experimental colitis did not modulate the activation kinetics of Na+ current in bladder DRG neurons but caused a leftward shift in inactivation curve from -37.75±3.64 mV to -47.62±1.5 mV (n=11, p≤0.05). CONCLUSIONS Our data provide evidence that acute experimental colitis can modify the expression of Na+ channels in bladder extrinsic sensory neurons via TRPV1 signaling pathways. This data can provide a basis for the development of new therapeutic protocols to treat chronic pelvic pain of genitourinary origin. Glenolden, PA© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e389-e390 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Qi Lei More articles by this author Xiao-Qing Pan More articles by this author Alan Wein More articles by this author Anna Malykhina More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...