• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Fatty acid amide hydrolase blockade attenuates the development of collagen-induced arthritis and related thermal hyperalgesia in mice.
【24h】

Fatty acid amide hydrolase blockade attenuates the development of collagen-induced arthritis and related thermal hyperalgesia in mice.

机译：脂肪酸酰胺水解酶的阻断减弱了小鼠胶原诱导的关节炎和相关的热痛觉过敏的发展。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Fatty acid amide hydrolase (FAAH) is the primary degradative enzyme of the endocannabinoid anandamide (N-arachidonoylethanolamine), which activates cannabinoid CB(1) and CB(2) receptors. FAAH disruption reduces nociception in a variety of acute rodent models of inflammatory pain. The present study investigated whether these actions extend to the chronic, collagen-induced arthritis (CIA) model. We investigated the anti-arthritic and anti-hyperalgesic effects of genetic deletion or pharmacological inhibition of FAAH in the CIA model. FAAH (-/-) mice, and FAAH-NS mice that express FAAH exclusively in nervous tissue, displayed decreased severity of CIA and associated hyperalgesia. These phenotypic anti-arthritic effects were prevented by repeated daily injections of the CB(2) receptor antagonist, SR144528, but not the CB(1) receptor antagonist rimonabant. Similarly, repeated administration of the FAAH inhibitor URB597 reduced CIA severity, and acute administration of rimonabant, but not SR144528, blocked the anti-hyperalgesic effects of prolonged FAAH inhibition, suggesting that prolonged CB(2) receptor activation reduces the severity of CIA, whereas acute CB(1) receptor activation reduces CIA-induced hyperalgesia. In contrast, acute administration of URB597 elicited a CB(1) receptor-dependent anti-hyperalgesic effect. The observed anti-arthritic and anti-hyperalgesic properties of FAAH inhibition, coupled with a lack of apparent behavioral alterations, suggest that endocannabinoid modulating enzymes offer a promising therapeutic target for the development of novel pharmacological approaches to treat rheumatoid arthritis and associated hyperalgesia.
机译：脂肪酸酰胺水解酶（FAAH）是内源性大麻素anandamide（N-花生四烯酸乙醇胺）的主要降解酶，可激活大麻素CB（1）和CB（2）受体。 FAAH破坏可减轻各种急性啮齿类动物炎性疼痛的伤害感受。本研究调查了这些作用是否扩展到慢性胶原诱导的关节炎（CIA）模型。我们调查了CIA模型中遗传缺失或FAAH的药理抑制作用的抗关节炎和抗痛觉过敏作用。仅在神经组织中表达FAAH的FAAH（-/-）小鼠和FAAH-NS小鼠显示出CIA和相关痛觉过敏的严重程度降低。通过每天重复注射CB（2）受体拮抗剂SR144528，而不是CB（1）受体拮抗剂利莫那班，可以防止这些表型抗关节炎作用。同样，反复给予FAAH抑制剂URB597可以降低CIA的严重程度，而利莫那班的急性给予（而不是SR144528）可以阻止FAAH长时间抑制的抗痛觉过敏作用，这表明延长CB（2）受体激活可以降低CIA的严重性。急性CB（1）受体激活减少了CIA诱导的痛觉过敏。相反，URB597的急性给药引起CB（1）受体依赖性抗痛觉过敏作用。观察到的抑制FAAH的抗关节炎和抗痛觉过敏特性，加上缺乏明显的行为改变，表明内源性大麻素调节酶为开发治疗风湿性关节炎和相关痛觉过敏的新型药理方法提供了有希望的治疗靶标。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号