NEUROLOGICAL BASIS OF PAIN--ROLE OF CANNABINOIDS

疼痛的神经学基础——大麻素的作用

• 批准号: 2271923
• 负责人: J. Michael Walker
• 金额: $ 18.19万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2271923
• 关键词: behavior test; cannabinoids; central neural pathway /tract; chemical stimulation; drug addiction antagonist; drug interactions; gene induction /repression; immunocytochemistry; laboratory rat; mathematical model; mechanical pressure; model design /development; neural transmission; neuropharmacology; pain; protooncogene; spinal cord; temperature; thalamus

The neurological basis of pain and the neural circuits that underlie pain perception and pain inhibition remain fundamental problems for neuroscientists. Much research in the past 25 years has focused on mechanisms in the brain that modulate pain sensitivity, especially those mechanisms related to the neurotransmitters and neuromodulators that control pain. This application addresses the possibility that endogenous ligands for the cannabinoid receptor play a significant role within neural circuits that modulate of pain sensitivity. The molecular basis for this hypothesis is the discovery and cloning of a G-protein coupled cannabinoid receptor and the identification of a putative endogenous ligand called anandamide. Because drugs of this class produce powerful inhibition of pain responses in animals, the possibility arises that the endogenous counterpart play a role in the neuronal mechanisms of pain inhibition. By delineating the functional role of cannabinoids, a better understanding of the neural basis of pain and pain inhibition would be achieved. The proposed experiments address the possibility that endogenous cannabinoid may play a role in the neurological basis of pain by examining the effects of cannbinoids on neural systems that are involved in pain processing. To assess these actions on pain pathways in the brain, an examination of the effects of cannabinoids on pain-evoked expression of c- fos like immunoreactivity i spinal cord is proposed. In a parallel line of research, an examination of the effects of cannabinoids on the firing of neurons in the thalamus and spinal cord is proposed. These experiments provide a means to build a theoretical model of the actions of endogenous cannabinoids within specific brain circuits that modify pain transmission. The studies may have clinical significance because they may provide a basis for estimating the efficacy of cannabinoids as a pharmacotherapy for pain.

疼痛和疼痛构成神经回路的神经系统基础 感知和疼痛抑制仍然是基本问题 神经科学家。 在过去的25年中，许多研究集中在 大脑中调节疼痛敏感性的机制，尤其是那些 与神经递质和神经调节剂有关的机制 控制疼痛。 该应用程序解决了内源性的可能性 大麻素受体的配体在神经中起着重要作用 调节疼痛敏感性的电路。 分子基础 假设是G蛋白耦合大麻素的发现和克隆 受体和假定的内源配体的鉴定称为 anandamide。 因为这类药物会产生强大的抑制 动物的疼痛反应，可能性是内源性的 对应物在疼痛抑制的神经元机制中起作用。 经过 描述大麻素的功能作用，更好地理解 将实现疼痛和疼痛抑制的神经基础。 提出的实验解决了内源性的可能性 大麻素可能通过检查在疼痛的神经学基础上发挥作用 大麻群对参与疼痛的神经系统的影响 加工。 为了评估大脑疼痛途径的这些行为， 检查大麻素对C-疼痛诱发表达的影响 提出了像免疫反应性I脊髓这样的FOS。 平行线 研究，检查大麻素对射击的影响 提出了丘脑和脊髓中的神经元。 这些实验 提供一种建立内源性行为的理论模型的方法 特定脑回路中的大麻素可以改变疼痛的传播。 这些研究可能具有临床意义，因为它们可能会提供基础 用于估计大麻素作为疼痛的药物疗法的功效。