Why cooling is beneficial: non-linear temperature-dependency of stimulated iCGRP release from isolated rat skin
Why cooling is beneficial: non-linear temperature-dependency of stimulated iCGRP release from isolated rat skin
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DOI：
10.1016/j.pain.2004.03.033
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发表时间：
2004-07-01
期刊：
影响因子：
7.4
通讯作者：
Reeh, PW
中科院分区：
文献类型：
--
作者：
Kichko, TI;Reeh, PW
伤害感受神经元中的辣椒素受体是致痛性炎症介质致敏作用的靶点。辣椒素和潜在的内源性配体被认为不是门控这种热激活的离子通道，而是使其如此深刻地敏感，以至于即使室温也可以打开它。我们研究了辣椒素诱导的CGRP从离体大鼠皮肤的伤害性神经纤维释放的温度依赖性，在一系列环境温度下，使用不同的激动剂浓度（10（-7）-10（-5）M）和KCl（60 mM）。为了控制环境温度（4-40 ℃）对基础iCGRP流出无显著影响。10（-6）M的超最大辣椒素浓度作为刺激物诱发的反应在温度从40 T降低到24 T时没有显著减弱，但在24 ℃和14 ℃之间其幅度损失了65%（Q（10）类似于6.7）。在较低的辣椒素浓度（10（-7）M）下，这种响应的崩溃发生在40 ℃和32 ℃之间。从40 ℃冷却至24 ℃时，浓度-反应曲线显示出明显的漂移，14 ℃时斜率和最大效应显著降低，这正式描述了非竞争性拮抗作用。KCl诱导的iCGRP释放显示出更线性的温度依赖性（Q（10）在24至14 ℃之间与2.4相似。即使在8摄氏度的显著辣椒素反应表明已知共表达CGRP和辣椒素受体的冷敏感神经元的贡献。热激活离子通道（TRPV 1 -4）被认为在炎性疼痛中起重要作用，通过冷却可以有效缓解炎性疼痛。目前的研究结果有助于理解这一现象。(C)2004年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
The capsaicin receptor in nociceptive neurons is a target for the sensitizing actions of algogenic inflammatory mediators. Capsaicin and potential endogenous ligands are thought not to gate this heat-activated ion channel but to sensitize it so profoundly that even room temperature can open it. We investigated the temperature dependency of capsaicin-induced CGRP release from nociceptive nerve fibers in isolated rat skin over a range of ambient temperatures using different agonist concentrations (10(-7)-10(-5) M) and KCl (60 mM) for control. Ambient temperature (4-40 degreesC) showed no significant influence on the basal iCGRP outflow. The supramaximal capsaicin concentration of 10(-6) M as a stimulus evoked a response that was not significantly diminished by temperatures decreasing front 40 to 24 T but lost 65% of its amplitude between 24 and 14 degreesC (Q(10) similar to 6.7). Such a collapse of the response occurred between 40 and 32 degreesC at lower capsaicin concentration (10(-7) M). The concentration-response curves showed a rightward shift upon cooling from 40 to 24 degreesC and a major loss of slope and maximum effect at 14 degreesC which formally describes a noncompetitive antagonism. KCl-induced iCGRP release showed a much more linear temperature dependency (Q(10) similar to 2.4 between 24 and 14 degreesC. Significant capsaicin responses even at 8 degreesC suggest a contribution of noxious-cold sensitive neurons known to coexpress CGRP and the capsaicin receptor. The heat-activated ion channels (TRPV1-4) are thought to play a significant role in inflammatory pain which is effectively relieved by cooling. The present results contribute to understanding this phenomenon. (C) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.