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伤害性信号传导的基础知识有限。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尚未明确定义。此外，关于TRPV1（一种主要的“疼痛”受体）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，但尚未严格定位。非特异性抗体标记和优先使用雄性啮齿动物是先前研究的主要局限性。该项目的目标是利用遗传小鼠模型来：1）在不同发育阶段精确地将伤害性神经输入映射到雄性和雌性小鼠膀胱，2）明确地将关键伤害性通道 TRPV1 和 TRPA1 的表达定位到神经和/或其他组织，以及 3）确认这些通道在已识别的细胞/组织层中的真实功能。最后，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.