Cannabinoid Modulation of Hyperalgesia

大麻素对痛觉过敏的调节

• 批准号: 6877367
• 负责人: Donald Simone
• 金额: $ 26.16万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-03 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6877367
• 关键词: afferent nerve; analgesics; calcium flux; cancer pain; cannabinoid receptor; cannabinoids; cyclic AMP; drug screening /evaluation; electrophysiology; heat stimulus; hyperalgesia; immunocytochemistry; laboratory mouse; local anesthetics; neoplastic growth; neuropharmacology; nociceptors; pharmacokinetics; receptor sensitivity; western blottings

DESCRIPTION (provided by applicant): Recent studies indicate that cannabinoids can produce antinociception, particularly in persistent pain conditions, through peripheral mechanisms. This is particularly interesting because targeting peripheral receptors for pain eliminates unwanted side effects associated with receptor activation if the central nervous system. Moreover, it has been suggested that cannabinoids may be more effective in conditions of persistent pain. In the proposed studies we will investigate the ability of cannabinoids to attenuate cancer pain. Cancer pain is a major problem for many patients and is often undermanaged. Using a model of cancer pain in mice in which sarcoma cells are implanted in and around the calcaneous bone, we will determine whether cannabinoids attenuate hyperalgesia when administered at the site of tumor growth (hind paw) and identify the receptor types involved through the use of receptor-selective agonists and antagonists. Mechanisms underlying peripheral cannabinoid antinociception will be investigated in electrophysiological and cellular studies. In Parallel of electrophysiological studies, we will determine if cannabinoids attenuate the sensitization of nociceptors that occurs during tumor growth. We will also investigate cellular events related to cannabinoid signaling that occur during tumor growth. We will determine whether cancer cells modify cannabinoid receptor expression and cannabinoid receptor signaling in primary afferent neurons.

描述（由申请人提供）：最近的研究表明，大麻素可以通过外围机制产生抗伤害感受，尤其是在持续的疼痛条件下。这特别有趣，因为靶向外围受体以消除与中枢神经系统（如果中枢神经系统）相关的不良副作用。此外，已经提出，大麻素在持续疼痛的条件下可能更有效。在拟议的研究中，我们将研究大麻素减轻癌症疼痛的能力。对于许多患者而言，癌症疼痛是一个主要问题，并且经常受到管理。使用肉瘤细胞植入钙骨和周围的小鼠中的癌症疼痛模型，我们将确定大麻素在肿瘤生长部位（Hind Paw）施用时是否会减弱痛觉过敏，并通过使用受体选择的激动剂和拮抗剂来识别涉及的受体类型。在电生理学和细胞研究中将研究外周外周蛋白抗伤害感受的机制。在电生理研究的同时，我们将确定大麻素是否会衰减肿瘤生长过程中发生的伤害感受器的敏化。我们还将研究与肿瘤生长过程中发生的大麻素信号传导有关的细胞事件。我们将确定癌细胞是否改变了原发性传入神经元中的大麻素受体表达和大麻素受体信号传导。