PAIN MODULATION BY ENDOGENOUS CANNABINOIDS

描述：（改编自研究者的摘要）拟议的研究 解决了大麻素受体内源性配体的可能性 在调节疼痛的神经回路中发挥重要作用 敏感性。该假说的分子基础是发现和 G蛋白偶联大麻素受体的克隆和鉴定 假定的内源性大麻素 anandamide。该实验室表明 合成大麻素注射到背部时会产生镇痛作用 导水管周围灰质 (PAG)，对该区域进行电刺激会产生 镇痛可以被大麻素拮抗剂阻断，这表明 镇痛是由内源性大麻素介导的。最近开发的一种方法 表明内源性大麻素 anandamide 在 PAG 中释放 这些刺激条件和后爪的有害刺激。的 提出的实验进一步检验了内源性的可能性 大麻素 anandamide 通过检查其释放在疼痛调节中发挥作用 在导水管周围灰质 (PAG) 中，该区域是已知的脑部区域 镇痛回路。将使用高微透析来测量释放 高效液相色谱/大气压化学电离质量 光谱测定法。基础释放，以及由有害刺激或刺激引起的释放 检查电去极化。实验将确定 周围纤维类型以及脊髓神经元和神经通路 诱导 anandamide 的释放。

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.