Cross-sensitization in the pelvis and neurogenic bladder

慢性盆腔疼痛是许多泌尿系统和胃肠道疾病的常见症状，包括间质性疼痛。 膀胱炎和肠易激综合征。盆腔器官间的交叉致敏作用导致慢性盆腔炎 病因不明的疼痛。我们的长期目标是阐明神经，神经体液和神经免疫 骨盆交叉致敏的潜在机制，并揭示其与 神经源性炎症和慢性盆腔疼痛。最近的研究表明感觉传入的作用 盆腔器官交叉致敏的途径，然而，我们对潜在机制的理解仍然是 基本的我们假设结肠炎症改变了膀胱的功能， 脊髓和背根神经节（DRG）中的传入感觉通路的敏化。我们建议 结肠炎症引起的DRG和脊髓感觉神经元兴奋性增强改变 促炎性神经肽的表达以及它们在膀胱中的释放，导致 后者发生神经源性炎症。神经解剖学，免疫组织化学， 将进行电生理学和神经药理学研究，以表征感觉神经元的作用。 结肠和膀胱之间交叉致敏的神经通路。具体目标是 对提出的假设进行全面评估。具体目标1将决定是否 结肠炎症改变感觉神经元脱敏前后膀胱背根节神经元的兴奋性 树脂毒素（RTX）。它还将解决RTX治疗对表达的影响， TRPV1、CGRP和SP在胸腰段和腰骶段DRG神经元中的表达。具体目标2将侧重于角色 辣椒素敏感的C纤维和Adelta纤维在伤害性结肠传入传入信息加工中的作用 和脊髓中的膀胱神经元。具体目标3将检验以下假设： 结肠或膀胱中的纤维阻止了实验后神经源性膀胱的发展， 诱发结肠炎。我们相信，揭示这些机制将导致新的治疗方法的发展。 可用于缓解泌尿生殖系统和胃肠道疾病患者慢性盆腔疼痛的方案 紊乱本项目将研究盆腔器官之间交叉致敏的神经体液机制， 揭示其与盆腔神经源性炎症和慢性盆腔疼痛的发生相关性。 这些机制的揭示将导致新的治疗方案的发展，可用于 缓解泌尿生殖系统和胃肠道疾病患者的慢性盆腔疼痛。

Chronic pelvic pain is a common symptom of many urologic and gastrointestinal disorders including interstitial cystitis and irritable bowel syndrome. Cross-sensitization among pelvic organs contributes to chronic pelvic pain of unknown etiology. Our long term goal is to elucidate the neural, neurohumoral and neuroimmune mechanisms underlying cross-sensitization in the pelvis and reveal its correlation with the occurrence of neurogenic inflammation and chronic pelvic pain. Recent studies demonstrated the role of sensory afferent pathways in pelvic organ cross-sensitization, however, our understanding of the underlying mechanisms is still rudimentary. We hypothesize that colonic inflammation alters the function of the urinary bladder due to sensitization of afferent sensory pathways in the spinal cord and dorsal root ganglia (DRG). We suggest that enhanced excitability of sensory neurons in the DRG and spinal cord induced by colonic inflammation alters the expression of pro-inflammatory neuropeptides as well as their release in the urinary bladder, leading to the development of neurogenic inflammation in the latter. Neuroanatomical, immunohistochemical, electrophysiological and neuropharmacological studies will be carried out to characterize the role of sensory neural pathways in cross-sensitization between the colon and urinary bladder. The specific aims are designed to provide a comprehensive assessment of the proposed hypothesis. Specific Aim 1 will determine whether colonic inflammation alters the excitability of bladder DRG neurons before and after desensitization of sensory afferents with resiniferatoxin (RTX). It will also address the effects of RTX treatment on the expression of TRPV1, CGRP and SP in thoracolumbar and lumbosacral DRG neurons. Specific Aim 2 will focus on the role of capsaicin-sensitive C- and Adelta-fibers in the processing of nociceptive colonic afferent input to convergent and bladder neurons in the spinal cord. Specific Aim 3 will test the hypothesis that desensitization of sensory fibers in the colon or urinary bladder prevents the development of a neurogenic bladder after experimentally induced colitis. We believe that uncovering these mechanisms will lead to the development of new therapeutic protocols that can be used to alleviate chronic pelvic pain in patients with genitourinary and gastrointestinal disorders. This project will study the neurohumoral mechanisms underlying the cross-sensitization among pelvic organs, reveal its correlation with the occurrence of neurogenic inflammation in the pelvis and chronic pelvic pain. Uncovering of these mechanisms will lead to the development of new therapeutic protocols that can be used to alleviate the chronic pelvic pain in patients with genitourinary and gastrointestinal disorders.