期刊
PAIN
卷 153, 期 1, 页码 86-94出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1016/j.pain.2011.09.021
关键词
Rostral ventromedial medulla; Descending facilitation; Cholecystokinin; Serotonin; PGE(2); Microdialysis; Tactile hypersensitivity; Nerve injury
资金
- National Institutes of Health/National Institute of Drug Abuse [R01-DA15205-01]
Cholecystokinin (CCK) has been suggested to be both pro-nociceptive and anti-opioid by actions on pain-modulatory cells within the rostral ventromedial medulla (RVM). One consequence of activation of RVM CCK2 receptors may be enhanced spinal nociceptive transmission; but how this might occur, especially in states of pathological pain, is unknown. Here, in vivo microdialysis was used to demonstrate that levels of RVM CCK increased by approximately 2-fold after ligation of L-5/L-6 spinal nerves (SNL). Microinjection of CCK into the RVM of naive rats elicited hypersensitivity to tactile stimulation of the hindpaw. In addition, RVM CCK elicited a time-related increase in (prostaglandin-E-2) PGE(2) measured in cerebrospinal fluid from the lumbar spinal cord. The peak increase in spinal PGE(2) was approximately 5-fold and was observed at approximately 80 minutes post-RVM CCK, a time coincident with maximal RVM CCK-induced mechanical hypersensitivity. Spinal administration of naproxen, a nonselective COX-inhibitor, significantly attenuated RVM CCK-induced hindpaw tactile hypersensitivity. RVM-CCK also resulted in a 2-fold increase in spinal 5-hydroxyindoleacetic acid (5-HIAA), a 5-hydoxytryptophan (5-HT) metabolite, as compared with controls, and mechanical hypersensitivity that was attenuated by spinal application of ondansetron, a 5-HT3 antagonist. The present studies suggest that chronic nerve injury can result in activation of descending facilitatory mechanisms that may promote hyperalgesia via ultimate release of PGE(2) and 5-HT in the spinal cord. (C) 2011 International Association for the Study of Pain. Published by Elsevier B. V. 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