Role of endogenous vanilloids and cannabinoids in pain

内源性香草素和大麻素在疼痛中的作用

• 批准号: 6930256
• 负责人: J. Michael Walker
• 金额: $ 34.09万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6930256
• 关键词: acyl group; analgesia; cannabinoid receptor; cannabinoids; capsaicin; chemical structure function; dopamine; drug receptors; edema; heat stimulus; hyperalgesia; inflammation; laboratory rat; neuropharmacology; neurophysiology; nociceptors; oxidation; pain

DESCRIPTION (provided by applicant): 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 research has been the elucidation of the biological effects of a family of lipid signalling molecules referred to 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 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.

描述（由申请人提供）：人体产生的促和抗伤害感性分子的研究可能会产生重要的靶标，以改善疼痛的治疗方法。最近且有希望的研究途径是阐明了被称为脂肪酸酰胺的脂质信号分子家族的生物学作用。提出的实验集中于N-酰胺胺的表征，N-酰胺胺是一种新型的脂肪酸酰胺，可以用作香草酸和/或大麻素受体的信号配体。由于大麻素受体的激活通常会抑制疼痛，而香草素受体的激活（例如，通过辣椒素）通常会增强对疼痛的敏感性，因此N-酰胺胺可能会内源性地发挥作用以促进或抑制疼痛。我们假设这些分子的作用取决于它们形成的位置和细胞环境的状态。因此，我们计划研究神经系统中各个部位的这些化合物的发生，以及各种生理和病理生理状况（例如炎症对它们的形成和生物活性）的影响。除了检查大麻素和香草素机制外，我们计划检查我们在体内观察到的NADA的氧化代谢产物。该提案旨在阐明内源性N-丙二胺及其氧化代谢物的生物学和功能，以增强我们对这一新兴分子类别的理解，这对于对疼痛的感知和调节可能很重要。对该系统的更好理解可能会产生用于治疗疼痛和/或炎症的药物开发的新型靶标。