Peripheral mechanisms of nociceptor modulation by NPY

描述：（由申请人提供）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）.许多研究评价了交感神经对伤害感受器的调制 利用典型地涉及外周痛觉过敏的动物模型， 神经损伤这些研究表明，NPY，一种交感神经， 衍生的神经肽，提供了一个重要的，但高度复杂的 周围神经损伤后的神经调节功能。然而，很少有研究 已经评估了在控制或“受伤”下伤害感受器的NPY调节 条件，这是本研究提案的广泛目标。我们认为 了解神经肽Y在基础条件下的功能对于 了解它如何应对伤害。具体目标是：1） 为了表征NPY受体激动剂的药理学作用， 调节神经源性炎症的起始; 2）确定是否 NPY受体激动剂抑制辣椒素诱发的痛觉过敏 3）评估施用到大鼠牙髓的分子基础; NPY药理学通过鉴定表达在细胞膜上的特异性NPY受体亚型， 辣椒素敏感类三叉神经感觉神经元和4），以评估 神经损伤对特定目标的影响#1-3。总的来说，这些参数， 综合和多学科的研究计划将被视为既解决 重要的科学问题，并提供一个极好的机会， 全面的科学训练。

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.