Vanilloid Receptors in Nociception

伤害感受中的香草酸受体

• 批准号: 6370603
• 负责人: JULI G VALTSCHANOFF
• 金额: $ 24.56万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-15 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6370603
• 关键词: C fiber; NMDA receptors; afferent nerve; capsaicin; cell cell interaction; confocal scanning microscopy; dorsal horn; dorsal root; drug receptors; electron microscopy; electrophysiology; glutamate receptor; immunocytochemistry; immunofluorescence technique; in situ hybridization; laboratory mouse; neural information processing; neurons; neuroregulation; pain; parabrachial nucleus; protein structure; substance K; substance P; synapses

The research aims at elucidating the role of vanilloid receptors (VR) in the mediation of nociception in the dorsal horn of mammals. Immunocytochemistry of the VR1 receptor has shown that this is expressed mainly in small cells of dorsal root ganglia and in afferents to the superficial laminae of the dorsal horn. VR1-immunopositive terminals predominate in lamina I and are present in lamina II. In this lamina, however, most of the staining for VR1 is in dendrites postsynaptic to primary afferents. It was also established that VR1 terminals do not contain substance P (SP). Thus, two main classes of afferents may mediate nociception and the question arises whether they contact the same neurons. This will be established by studying, with confocal microscopy and electron microscopy, whether VR1- and SP-immunopositive terminals contact the same neuron expressing neurokinin receptors (NK1) in lamina I. It is predicted that, if VR1-positive afferents mediate nociception, these neurons will project to the parabrachial nucleus, a major destination for ascending nociceptive pathways in rodents. The research will also establish what glutamate receptor subunits are present at VR1-positive synapses in superficial laminae. In particular, the absence of NMDA receptor would signify a clearly different role for these synapses from that of afferents that release SP. Also this part of the research will require simultaneous multiple labeling at the light and electron microscopic level. The third aim of the research is to test whether postsynaptic VR1 is related to activity in C fibers, independently from its origin, i.e. from intrinsic neurons or via transsynaptic traffic. The total depletion of VR1 in the dorsal horn after dorsal rhizotomy suggests an activity dependency of postsynaptic VR1 and this will be tested by conduction block of dorsal roots and, conversely, by selective activation of C fibers with cutaneous application of mustard oil.

该研究旨在阐明香草素受体（VR）在哺乳动物背角的伤害感受中的作用。 VR1受体的免疫细胞化学表明，这主要在背根神经节的小细胞和对背角表面层状的传入中表达。 VR1 - 免疫阳性末端在薄片I中占主导地位，并且存在于Lamina II中。 然而，在这种薄片中，VR1的大多数染色都是在降突触后对主要传入的染色体。 还确定VR1终端不包含P（SP）物质。 因此，两个主要传入可能会介导伤害感受，并且问题是否与同一神经元接触。 This will be established by studying, with confocal microscopy and electron microscopy, whether VR1- and SP-immunopositive terminals contact the same neuron expressing neurokinin receptors (NK1) in lamina I. It is predicted that, if VR1-positive afferents mediate nociception, these neurons will project to the parabrachial nucleus, a major destination for ascending nociceptive pathways在啮齿动物中。 这项研究还将确定在表面薄片中的VR1阳性突触中存在哪些谷氨酸受体亚基。 特别是，NMDA受体的不存在将表示这些突触与释放sp的传入的作用明显不同。 同样，研究的这一部分将需要在光和电子显微镜水平上同时进行多重标记。 该研究的第三个目的是测试突触后VR1是否与C纤维的活性有关，与其起源，即来自固有神经元或通过跨性别交通相关。 背根茎切开术后VR1的总VR1的总耗竭表明突触后VR1的活性依赖性，这将通过背根的传导阻滞来对其进行测试，相反，通过选择性地激活C纤维在皮肤上施用芥末油。