Role of endogenous vanilloids and cannabinoids in pain

对身体产生的亲伤害感受分子和抗伤害感受分子的研究可能会产生重要的靶点， 改善疼痛治疗。一个最近的和有前途的研究途径是阐明 脂肪酸酰胺类脂质信号分子家族的生物学效应。拟议 实验集中于N-酰基多巴胺的表征，N-酰基多巴胺是一组新的脂肪酸酰胺， 作为香草素和/或大麻素受体的信号配体。由于大麻素的激活 辣椒素受体通常抑制疼痛，而香草素受体的激活（例如通过辣椒素）通常 1 增加对疼痛的敏感性，N-酰基多巴胺可以内源性地促进或抑制疼痛。我们 假设这些分子的作用取决于它们形成的位置和它们的分子结构。 细胞环境的状态。因此，我们计划调查这些化合物的发生情况， 神经系统内的各种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。除了检查大麻素和 香草素机制，我们计划检查我们在体内观察到的NADA的含氧代谢产物。的 该提案旨在阐明内源性N-酰基多巴胺及其氧化产物的生物学和功能。 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。更好地了解这个系统可能会产生新的 用于治疗疼痛和/或炎症的药物开发的靶点。

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.