Peripheral mechanisms of nociceptor modulation by NPY

描述：(申请人提供)交感神经系统有助于 某些类型的慢性疼痛状态，如复杂的区域疼痛综合征 (CRPS)。许多研究已经评估了伤害性感受器的交感调制 利用痛觉过敏的动物模型，通常涉及外周 神经损伤。这些研究表明，NPY是一种富有同情心的 衍生神经肽，提供了一种重要的尽管高度复杂的 周围神经损伤后的神经调节功能。然而，很少有研究 评估了伤害性感受器在受控或“损伤内”的NPY调制 条件，这是本研究提案的广泛目标。我们相信 了解NPY在基本条件下如何发挥作用对于 了解它如何在受伤时发挥作用。具体目标是：1) 研究神经肽Y受体激动剂的药理作用 调节神经源性炎症的启动；2)确定 NPY受体激动剂抑制辣椒素引起的痛觉过敏 对大鼠牙髓的给药；3)评价其分子基础 通过鉴定神经肽Y受体亚型表达的神经肽Y药理学 辣椒素敏感类三叉神经感觉神经元和4)评估 神经损伤对特定目标#1-3的影响。总的来说，这些参数， 综合和多学科研究计划将既解决 这是一个重要的科学问题，并为 全面科学训练。

DESCRIPTION: (provided by applicant) The sympathetic nervous system contributes to certain types of chronic pain states such as complex regional pain syndrome (CRPS). Many studies have evaluated sympathetic modulation of nociceptors utilizing animal models of hyperalgesia that typically involve a peripheral nerve injury. These studies have demonstrated that NPY, a sympathetically derived neuropeptide, provides an important although highly complex neuromodulatory function after peripheral nerve injury. However, few studies have evaluated NPY modulation of nociceptors under control or "in-injured" conditions, which is the broad objective of this research proposal. We believe that understanding how NPY functions under basal conditions is critical to understanding how it functions in response to injury. The specific aims are: 1) to characterize the pharmacological effects of NPY receptor agonists for modulating the initiation of neurogenic inflammation; 2) to determine whether NPY receptor agonists inhibit capsaicin-evoked hyperalgesia following administration to the rat dental pulp; 3) to evaluate the molecular basis for NPY pharmacology by identifying specific NPY receptor subtypes expressed on the capsaicin-sensitive class of trigeminal sensory neurons and 4) to evaluate the effects of nerve injury on specific aims #1-3. Collectively, these parametric, integrated and multidisciplinary research plan will seen to both address an important scientific question, and to provide an excellent opportunity for comprehensive scientific training.