Nociceptive Innervation and Receptors in the Bladder

描述（由申请人提供）：膀胱疼痛综合征是常见的，特别是在女性中普遍存在。治疗膀胱疼痛的问题之一是我们对膀胱中伤害性信号的基本知识有限。例如，膀胱中的伤害神经支配和关键伤害感觉受体的精确定位尚未得到很好的定义。此外，关于主要的“疼痛”受体TRPV1是否在膀胱尿路上皮中表达，存在相当大的争议。TRPA1是另一个重要的伤害感受通道，已在膀胱中发现，但没有严格定位。非特异性抗体标记和优先使用雄性啮齿动物是以往研究的主要局限性。本项目的目标是利用小鼠遗传模型：1)精确定位不同发育阶段雄性和雌性小鼠膀胱的伤害神经输入；2)明确定位关键伤害神经通道TRPV1和TRPA1在神经和/或其他组织中的表达；3)在鉴定的细胞/组织层中确认这些通道的骨功能。在结论中，我们将能够向GUDMAP提交TRPV1基因谱系、TRPV1和TRPA1在膀胱中相对于特定组织锚定基因的表达。

DESCRIPTION (provided by applicant): Bladder pain syndromes are common and especially prevalent in women. One of the problems in treating bladder pain is that our fundamental knowledge of nociceptive signaling in the bladder is limited. For example, nociceptive innervation in the bladder and the precise localization of key nociceptive receptors are not well defined. Further, there is considerable controversy as to whether TRPV1, a major "pain" receptor, is expressed in the bladder urothelium. TRPA1, another important nociceptive channel, has been identified in bladder but not rigorously localized. Non-specific antibody labeling, and the preferential use of male rodents are major limitations of previous studies. The goal of this project is to exploit genetic mouse models to: 1) precisely map nociceptive nerve input to the male and female mouse bladder at different developmental stages, 2) unambiguously localize expression of key nociceptive channels, TRPV1 and TRPA1, to nerves and/or other tissues, and 3) confirm bone fide function of these channels in identified cells/tissu layers. At the conclusion we will be able to submit to GUDMAP the expression of the TRPV1 gene lineage, TRPV1 and TRPA1 in bladder relative to specific tissue anchor genes.