C2 spinal cord stimulation induces dynorphin release from rat T4 spinal cord: potential modulation of myocardial ischemia-sensitive neurons
C2 spinal cord stimulation induces dynorphin release from rat T4 spinal cord: potential modulation of myocardial ischemia-sensitive neurons
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DOI：
10.1152/ajpregu.00899.2007
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发表时间：
2008-11-01
影响因子：
2.8
通讯作者：
Williams, Carole A.
中科院分区：
文献类型：
--
作者：
Ding, XiaoHui;Hua, Fang;Williams, Carole A.
在心肌缺血期间，颅颈脊髓（C1-C2）调节心脏伤害性信号的中枢处理。本研究旨在确定：1）C2 SCS是否诱导胸（T4）脊髓背角中镇痛神经肽的释放; 2）该镇痛肽的来源之一是否为颈固有脊髓神经元; 3）C2神经元的化学失活是否在同时发生的C2 SCS和心脏缺血期间改变局部T4 P物质（SP）释放。通过间歇性阻塞麻醉的Sprague-Dawley大鼠的冠状动脉左前降支（CoAO）诱导缺血。强啡肽A（1-13）、（DYN）和SP的释放使用插入T4的抗体包被的微探针测定。SCS单独诱导T4中I-V层的DYN释放，并且在CoAO期间维持这种释放。C2注射兴奋毒素，鹅膏蕈氨酸，在SCS之前，抑制T4 DYN释放在SCS和缺血;它也逆转了SP释放从T4背侧板在C2 SCS和CoAO的抑制。在SCS和CoAO期间，向T4中注射κ-阿片样物质拮抗剂nor-binaltorphimine也允许增加SP释放。CoAO增加了T4背角中Fos阳性神经元的数量，但不增加中间外侧柱（IML）中的Fos阳性神经元的数量，而SCS（单独或在CoAO期间）最大限度地减少了对CoAO单独的背角反应，同时诱导T4 IML神经元募集。这些结果表明，颈部脊髓固有通路的激活诱导DYN释放在胸脊髓，从而调制来自缺血心脏的伤害性信号。
During myocardial ischemia, the cranial cervical spinal cord (C1-C2) modulates the central processing of the cardiac nociceptive signal. This study was done to determine 1) whether C2 SCS-induced release of an analgesic neuropeptide in the dorsal horn of the thoracic (T4) spinal cord; 2) if one of the sources of this analgesic peptide was cervical propriospinal neurons, and 3) if chemical inactivation of C2 neurons altered local T4 substance P (SP) release during concurrent C2 SCS and cardiac ischemia. Ischemia was induced by intermittent occlusion of the left anterior descending coronary artery (CoAO) in urethane-anesthetized Sprague-Dawley rats. Release of dynorphin A (1-13), (DYN) and SP was determined using antibody-coated microprobes inserted into T4. SCS alone induced DYN release from laminae I-V in T4, and this release was maintained during CoAO. C2 injection of the excitotoxin, ibotenic acid, prior to SCS, inhibited T4 DYN release during SCS and ischemia; it also reversed the inhibition of SP release from T4 dorsal laminae during C2 SCS and CoAO. Injection of the kappa-opioid antagonist, nor-binaltorphimine, into T4 also allowed an increased SP release during SCS and CoAO. CoAO increased the number of Fos-positive neurons in T4 dorsal horns but not in the intermediolateral columns (IML), while SCS (either alone or during CoAO) minimized this dorsal horn response to CoAO alone, while inducing T4 IML neuronal recruitment. These results suggest that activation of cervical propriospinal pathways induces DYN release in the thoracic spinal cord, thereby modulating nociceptive signals from the ischemic heart.