PAIN MODULATION BY ENDOGENOUS CANNABINOIDS

描述：(改编自《调查者摘要》)拟议的研究 解决了内源性大麻素受体配体 在调节疼痛的神经回路中扮演着重要的角色 敏感度。这一假说的分子基础是发现和 G蛋白偶联大麻素受体基因的克隆及鉴定 推定的内源性大麻素A-ANANDAME。这个实验室表明 合成大麻素在背部注射时产生止痛作用 导水管周围灰质(PAG)，电刺激该区域产生 可被大麻素拮抗剂阻断的止痛作用 镇痛作用是由内源性大麻素介导的。一种最新开发的方法 提示内源性大麻素脱氢酶在下丘脑PAG内释放。 这些刺激条件和对后爪的有害刺激。这个 拟议中的实验进一步检验了内源性 大麻素胺通过检测其释放而在痛觉调制中发挥作用 在导水管周围灰质(PAG)，已知的大脑区域是 止痛电路。释放度将使用高含量的微透析法进行测量 高效液相色谱/大气压化学电离质量 光谱分析。基础释放和由有害刺激或刺激刺激的释放 对电除极化进行了研究。这些实验将决定 外周纤维类型与脊髓神经元和神经通路 诱导脱氢表雄胺的释放。

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.