34 MECHANISMS INDUCING AUTONOMIC DYSREFLEXIA DURING BLADDER DISTENTION IN RATS WITH SPINAL CORD INJURY

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research (1)1 Apr 201334 MECHANISMS INDUCING AUTONOMIC DYSREFLEXIA DURING BLADDER DISTENTION IN RATS WITH SPINAL CORD INJURY Tsuyoshi Yoshizawa, Satoru Yoshikawa, Ryosuke Takahashi, Satoru Takahashi, and Naoki Yoshimura Tsuyoshi YoshizawaTsuyoshi Yoshizawa Pittsburgh, PA More articles by this author , Satoru YoshikawaSatoru Yoshikawa Pittsburgh, PA More articles by this author , Ryosuke TakahashiRyosuke Takahashi Pittsburgh, PA More articles by this author , Satoru TakahashiSatoru Takahashi Tokyo, Japan More articles by this author , and Naoki YoshimuraNaoki Yoshimura Pittsburgh, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1409AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Autonomic dysreflexia (AD) is a potentially life-threatening medical emergency, and can be induced by viscero-vascular reflexes during bladder distention, resulting in uncontrolled sympathetic activity and hypertension, in patients with spinal cord injury (SCI). This study investigated the mechanisms inducing AD in SCI due to enhanced bladder-to-vascular reflexes in rats, especially focusing on capsaicin-sensitive C-fiber afferents and nerve growth factor (NGF) expression. METHODS SCI was produced by transection of the Th4-5 spinal cord in female rats. After 4 weeks, changes in blood pressure during graded increases in intravesical pressure (20 to 80 cmH2O) were measured in spinal intact (SI) and SCI rats under urethane anesthesia. In some animals, effects of C-fiber desensitization induced by capsaicin-pretreatment (125mg/kg, s.c.) on the bladder-to-vascular reflex were also examined. NGF levels of mucosa and detrusor muscle layers of the bladder, and L6-S1 dorsal root ganglia (DRG) were measured by RT-PCR and ELISA. Patch-clamp recordings were also performed in capsaicin-sensitive bladder afferent neurons dissociated from L6-S1 DRG, which were labeled by Fast Blue injected into the bladder wall. RESULTS In SI and SCI rats, systemic arterial blood pressure was increased in pressure-dependent fashion during increases in intravesical pressure, with blood pressure elevation started at lower intravesical pressure (20 cmH2O) in SCI rats compared to SI rats. In addition, these arterial blood pressure responses to bladder distention were significantly reduced by desensitization of capsaicin-sensitization C-fiber afferent pathways. Patch-clamp recordings showed hyperexcitability of bladder afferent neurons from SCI rats as evidenced by lower thresholds for action potential activation in SCI rats compared to SI rats (−26.4±1.3 vs. −21.8±0.9mV). SCI rats also had higher NGF mRNA and protein levels of the bladder and DRG compared to SI rats. CONCLUSIONS These results indicate that the bladder-to-vascular reflex induced by capsaicin-sensitive C-fiber afferents is enhanced in association with increased NGF expression after SCI, suggesting that suppression of C-fiber bladder afferent activity and/or NGF expression in the bladder could be effective for reducing AD episodes during bladder distention in patients with SCI. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e13-e14 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tsuyoshi Yoshizawa Pittsburgh, PA More articles by this author Satoru Yoshikawa Pittsburgh, PA More articles by this author Ryosuke Takahashi Pittsburgh, PA More articles by this author Satoru Takahashi Tokyo, Japan More articles by this author Naoki Yoshimura Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...