PAIN MODULATION BY ENDOGENOUS CANNABINOIDS

内源性大麻素的疼痛调节

• 批准号: 7004889
• 负责人: J. Michael Walker
• 金额: $ 11.52万
• 依托单位: TRUSTEES OF INDIANA 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 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7004889
• 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：（改编自研究者摘要）拟议的研究 解决了大麻素受体的内源性配体 在调节疼痛的神经回路中起着重要作用 灵敏度这一假说的分子基础是发现， G-蛋白偶联大麻素受体的克隆和 假定的内源性大麻素anandamide。这个实验表明， 当在背部注射合成大麻素时， 中脑导水管周围灰质（PAG），电刺激该区域产生 镇痛，可以阻断大麻素拮抗剂，这表明， 镇痛作用由内源性大麻素介导。最近开发的一种方法 表明内源性大麻素anandamide在PAG中释放， 这些刺激条件和对后爪的有害刺激。的 建议的实验进一步研究的可能性， 大麻素anandamide通过检测其释放在疼痛调节中起作用 在中脑导水管周围灰质（PAG），一个已知是大脑中的一部分的大脑区域， 镇痛回路释放将使用具有高浓度的微透析来测量。 高效液相色谱/大气压化学电离质谱 光谱法基础释放，以及由伤害性刺激或 检查电去极化。这些实验将决定 外周纤维类型和脊髓神经元和神经通路， 诱导大麻素的释放