PAIN MODULATION BY ENDOGENOUS CANNABINOIDS

内源性大麻素的疼痛调节

• 批准号: 6350539
• 负责人: J. Michael Walker
• 金额: $ 30.58万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-25 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6350539
• 关键词: C fiber; G protein; analgesia; anandamide; biological signal transduction; brain mapping; cannabinoid receptor; cannabinoids; electrophysiology; electrostimulus; high performance liquid chromatography; immunocytochemistry; injection /infusion; intravenous administration; liquid chromatography mass spectrometry; microdialysis; neuroanatomy; neurons; neuroregulation; pain; periaqueductal gray matter; receptor coupling; spinal cord

DESCRIPTION: (Adapted from the Investigator's Abstract) The proposed research addresses the possibility that endogenous ligands for the cannabinoid receptor play a significant role within the neural circuits that modulate pain sensitivity. The molecular basis for this hypothesis is the discovery and cloning of a G-protein coupled cannabinoid receptor and the identification of the putative endogenous cannabinoid anandamide. This laboratory showed that synthetic cannabinoids produce analgesia when injected in the dorsal periaquaductal gray (PAG), and electrical stimulation of this area produces analgesia that can be blocked by a cannabinoid antagonist suggesting that the analgesia is mediated by an endogenous cannabinoid. A recently developed method indicated the endogenous cannabinoid anandamide is released in the PAG under these stimulation conditions and upon noxious stimulation of the hindpaws. The proposed experiments further examine the possibility that the endogenous cannabinoid anandamide plays a role in pain modulation by examining its release in the periaquaductal gray (PAG), a brain region known to be part of an analgesic circuit. Release will be measured using microdialysis with high performance liquid chromatography/atmospheric pressure chemical ionization mass spectrometry. Basal release, and release stimulated by noxious stimulation or electrical depolarization are examined. The experiments will determine the peripheral fiber types and the spinal cord neurons and neural pathways that induce the release of anandamide.

描述：（根据调查员的摘要改编）拟议的研究 解决了大麻素受体内源配体的可能性 在调节疼痛的神经回路中发挥重要作用 灵敏度。该假设的分子基础是发现和 G蛋白耦合大麻素受体的克隆和鉴定 假定的内源性大麻蛋白枪。这个实验室表明 当在背侧注射时，合成大麻素会产生镇痛 周围灰色（PAG）和该区域的电刺激产生 可以通过大麻素拮抗剂阻止的镇痛表明 镇痛是由内源性大麻素介导的。最近开发的方法 指示内源性大麻素配胺在PAG中释放 这些刺激条件和后爪的有害刺激。这 提出的实验进一步研究了内源性的可能性 大麻素配胺通过检查其释放在疼痛调制中起作用 在妊娠灰色（PAG）中，已知是大脑区域 镇痛电路。释放将使用高的微透析测量 性能液相色谱/大气压化学电离质量 光谱法。基础释放，并受到有害刺激或刺激的释放 检查电去极化。实验将确定 外围纤维类型以及脊髓神经元和神经途径 诱导anandamide的释放。