NEURAL AND MOLECULAR MECHANISMS OF HYPERALGESIA

痛觉过敏的神经和分子机制

• 批准号: 2882591
• 负责人: DAVID J MAYER
• 金额: $ 15.43万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2882591
• 关键词: chronic pain; drug tolerance; glutamate receptor; hyperalgesia; laboratory rat; morphine; nitric oxide; opioid receptor; pain threshold; protein kinase C; temperature; chronic pain; drug tolerance; glutamate receptor; hyperalgesia; laboratory rat; morphine; nitric oxide; opioid receptor; pain threshold; protein kinase C; temperature

The goal of this research project is to understand neural and molecular mechanisms of thermal hyperalgesia associated with narcotic tolerance. Recent investigations have indicated that thermal hyperalgesia develops in association with the development of narcotic tolerance and that excitatory amino acid (EAA) receptor activation and subsequent intracellular second messenger systems may play a critically important role in central nervous system mechanisms of thermal hyperalgesia associated with narcotic tolerance. Thus, multidisciplinary approaches including behavioral, pharmacological, autoradiographic, and immunocytochemical methods will be used to accomplish 3 specific aims: (l) To clarify the time course and dose-response relationships of morphine treatment as well as the role of the opiate kappa receptor in the development of thermal hyperalgesia associated with narcotic tolerance; (2) To determine the role of EAA receptors (both ionotropic and metabotropic EAA receptors) and their relationships in the development and expression of the thermal hyperalgesia; and (3) To determine the role of EAA receptor mediated changes in intracellular protein kinase C and nitric oxide and their relationships in the development and expression of the thermal hyperalgesia. This proposed work will provide novel and important information on neural and molecular mechanisms of hyperalgesia that may be common to thermal hyperalgesia associated with the development of narcotic tolerance in particular and with neurogenic and inflammatory etiologies in general. Because of the intimate relationship between narcotic tolerance and associated thermal hyperalgesia as well as potential interrelations between hyperalgesia induced by narcotic treatment and nerve (tissue) injury or inflammation, the results of this work may help to improve clinical utility of narcotic analgesics in treatment of chronic pain states. In addition, the results from assessment of the roles of EAA receptors, protein kinase C, and nitric oxide will provide insights into the neurobiology of narcotic tolerance which could result in additional clinical applications.

该研究项目的目的是了解神经和分子 与麻醉耐受性相关的热痛觉过敏的机制。 最近的调查表明，热痛觉过敏 与麻醉耐受性的发展和兴奋性相关 氨基酸（EAA）受体激活和随后的细胞内第二 Messenger系统可能在中枢神经中起着至关重要的作用 与麻醉有关的热痛觉过敏的系统机制 宽容。因此，包括行为的多学科方法， 药理学，放射自显影和免疫细胞化学方法将是 用于完成3个具体目标：（l）阐明时间课程和 吗啡治疗的剂量反应关系以及 鸦片kappa受体在热痛觉的发展中 与麻醉耐受性有关； （2）确定EAA的作用 受体（离子型和代谢性EAA受体）及其受体 热的发展和表达的关系 痛风； （3）确定EAA受体介导的作用 细胞内蛋白激酶C和一氧化氮及其的变化 热的发展和表达的关系 痛苦。这项拟议的工作将提供新颖而重要的 有关痛觉过敏的神经和分子机制的信息 与麻醉性发展有关的热痛觉过敏 尤其是耐受性，以及神经源性和炎症病因 一般的。由于麻醉耐受性之间的亲密关系 以及相关的热痛觉和潜在的相互关系 在麻醉治疗和神经（组织）引起的痛觉过敏之间 受伤或炎症，这项工作的结果可能有助于改善 麻醉镇痛药治疗慢性疼痛的临床效用 国家。此外，评估EAA角色的结果 受体，蛋白激酶C和一氧化氮将提供洞察力 麻醉耐受性的神经生物学可能导致额外 临床应用。