Role of endogenous vanilloids and cannabinoids in pain

对身体产生的促痛和抗伤害性分子的研究可能会产生重要的靶点 改善了疼痛的治疗。最近一个很有前途的研究途径是阐明 脂肪酸酰胺类脂类信号分子的生物学效应。建议数 实验集中在N-酰基多巴胺的表征上，N-酰基多巴胺是一种新的脂肪酸酰胺类化合物，可以 作为香草素和/或大麻素受体的信号配基。由于大麻素的激活 受体通常抑制疼痛，而香草素受体的激活(如辣椒素)通常 1 增加对疼痛的敏感性，N-酰基多巴胺可能内源性地起到促进或抑制疼痛的作用。我们 假设这些分子的作用取决于它们形成的位置和 蜂窝环境的状态。因此，我们计划调查这些化合物在 神经系统内的不同部位以及各种生理和病理生理学的影响 炎症等条件对其形成和生物活性的影响。除了检测大麻素和 香草素机制，我们计划检查我们在体内观察到的NADA的氧化代谢物。这个 该提案旨在阐明内源性N-酰基多巴胺及其氧合的生物学和功能 代谢物，以加强我们对这类新兴分子的理解，这可能是 对疼痛的感知和调节很重要。更好地理解这一系统可能会产生新的 旨在治疗疼痛和/或炎症的药物开发的目标。

The study of pro- and anti-nociceptive molecules produced by the body may yield important targets for improved treatments of pain. A recent and promising avenue of researchhas been the elucidation of the biological effects of a family of lipid signalling molecules referredto as fatty acid amides. The proposed experiments focus on the characterization of N-acyldopamines, a novel group of fatty acid amides that may serve as signalling ligands for the vanilloid and/or cannabinoid receptors. Since activation of cannabinoid receptors typically suppresses pain, while activation of vanilloid receptors (e.g. by capsaicin) typically 1 heightens sensitivity to pain, N-acyldopamines may serve endogenously to facilitate or dampen pain. We hypothesize that the actions of these molecules depend on the locations at which they are formed and the state of the cellular environment. Hence, we plan to investigate the occurrence of these compounds at various sites within the nervous system and the effect of various physiological and pathophysiological conditions such as inflammation on their formation and bioactivity. In addition to examining cannabinoid and vanilloid mechanisms, we plan to examine oxygenated metabolites of NADA that we observed in vivo. The proposal aims to elucidate the biology and function of endogenous N-acyldopamines and their oxygenated metabolites in order to enhance our understanding of this emerging class of molecules, which may be important to the perception and modulation of pain. A better understanding of this system may yield novel targets for drug development aimed at treating pain and/or inflammation.