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: 7485422
• 负责人: J. Michael Walker
• 金额: $ 3.75万
• 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/7485422
• 关键词: Acids; Address; Affinity; Amides; Arachidonic Acids; Binding; Biological; Biological Assay; Biology; Bos taurus; Brain; Cannabinoids; Capsaicin; Carrageenan; Cattle; Cells; Chemicals; Class; Condition; Corpus striatum structure; Cytochrome P450; Data; Dopa; Dopamine; Edema; Endocannabinoids; Environment; Enzymes; Family; Fatty Acids; Fire - disasters; Goals; Hyperalgesia; Inflammation; Inflammatory; Injection of therapeutic agent; Knockout Mice; Laboratories; Left; Leukotriene Receptor; Leukotrienes; Ligands; Lipids; Lipoxygenase; Location; Mechanical Stimulation; Mediating; Mining; Molecular; Nervous system structure; Neurons; Nociception; Numbers; Pain; Pathway interactions; Perception; Pharmacology; Pharmacotherapy; Physiological; Play; Property; Prostaglandin-Endoperoxide Synthase; Public Health; Research; Response to stimulus physiology; Rodent; Role; Signal Pathway; Signal Transduction; Signaling Molecule; Site; Skin; Spinal; Spinal Cord; Spinal Ganglia; Structure; Structure-Activity Relationship; System; TRPV1 gene; Tissues; Vanilloid; Walkers; anandamide; base; cannabinoid receptor; capsaicin receptor; cyclooxygenase 1; drug development; improved; in vivo; midbrain central gray substance; novel; pain inhibition; receptor; relating to nervous system; research study; size

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.

对机体产生的亲痛觉分子和抗痛觉分子的研究可能会产生重要的靶点