期刊
NEUROPHARMACOLOGY
卷 62, 期 4, 页码 1746-1755出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2011.11.021
关键词
Transient receptor potential vanilloid type 1 (TRPV1); Cannabinoid type 1 receptor (CB1); Anandamide (AEA); Neuropathic pain; Spinal cord; Fatty acid amide hydrolase (FAAH)
资金
- Dept. of Pain, Ministry of Science and Higher Education, Warsaw, Poland
- Dept. of Pharmacology, Ministry of Science and Higher Education, Warsaw, Poland
- Foundation for Polish Science and Iceland, Liechtenstein and Norway through the EEA Financial Mechanism
- NIH [DA009789]
The endocannabinoid anandamide (AEA) activates also transient receptor potential vanilloid-1 (TRPV1) channels. However, no data exist on the potential role of spinal TRPV1 activation by AEA in neuropathic pain. We tested the effect of: 1) AEA (5-100 mu g), alone or in the presence of an inhibitor of its hydrolysis, and 2) elevated levels of endogenous AEA (following inhibition of AEA hydrolysis), in CCI rats, and the involvement of TRPV1 or cannabinoid CB1 receptors in the observed effects. Levels of AEA in the spinal cord of CCI rats were measured following all treatments. AEA (50 mu g) displayed anti-allodynic and anti-hyperalgesic effects which were abolished by previous antagonism of TRPV1, but not CB1, receptors. Depending on the administered dose, the selective inhibitor of AEA enzymatic hydrolysis, URB597 (10-100 mu g), reduced thermal and tactile nociception via CB1 or CB1/TRPV1 receptors. The anti-nociceptive effects of co-administered per se ineffective doses of AEA (5 mu g) and URB597 (5 mu g) was abolished by antagonism of CB1, but not TRPV1, receptors. Spinal AEA levels were increased after CCI, slightly increased further by URB597, 10 mu g it., and strongly elevated by URB597, 100 mu g. Injection of AEA (50 mu g) into the lumbar spinal cord led to its dramatic elevation in this tissue, whereas, when a lower dose was used (5 mu g) AEA endogenous levels were elevated only in the presence of URB597 (5 mu g). We suggest that spinal AEA reduces neuropathic pain via CB1 or TRPV1, depending on its local concentration. (c) 2011 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据