Nociceptive Innervation and Receptors in the Bladder

描述(申请人提供)：膀胱痛综合征是常见的，尤其是在妇女中流行。治疗膀胱痛的问题之一是我们对膀胱伤害性信号的基础知识有限。例如，膀胱中的伤害性神经支配和关键伤害性感受器的精确定位并不是很清楚。此外，关于TRPV1这一主要的疼痛受体是否在膀胱尿路上皮细胞中表达也存在相当大的争议。TRPA1是另一个重要的伤害性感受通道，已在膀胱中发现，但定位不严格。非特异性抗体标记，以及优先使用雄性啮齿动物是先前研究的主要局限性。本项目的目标是利用遗传小鼠模型来：1)准确地将伤害性神经输入定位到不同发育阶段的雄性和雌性小鼠的膀胱；2)明确地定位关键的伤害性感受通道TRPV1和TRPA1在神经和/或其他组织中的表达；3)确认这些通道在已确定的细胞/组织层中的骨真实功能。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.