Nociceptive Innervation and Receptors in the Bladder

描述（由申请人提供）：膀胱疼痛综合征很常见，尤其是在女性中。治疗膀胱疼痛的问题之一是我们对膀胱中的伤害性信号传导的基本知识是有限的。例如，膀胱中的伤害性神经支配和关键伤害性受体的精确定位还没有很好地定义。此外，有相当大的争议，是否TRPV 1，一个主要的“疼痛”受体，表达在膀胱尿路上皮。TRPA 1是另一个重要的伤害性通道，已在膀胱中被鉴定，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前研究的主要局限性。该项目的目标是利用遗传小鼠模型：1）在不同发育阶段将伤害性神经输入精确映射到雄性和雌性小鼠膀胱，2）明确定位关键伤害性通道TRPV 1和TRPA 1在神经和/或其他组织中的表达，以及3）确认这些通道在识别的细胞/组织层中的真正功能。最后，我们将能够向GUDMAP提交TRPV 1基因谱系、TRPV 1和TRPA 1在膀胱中相对于特定组织锚基因的表达。

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.