Differential regulation of peripheral IL-1β-induced mechanical allodynia and thermal hyperalgesia in rats
Differential regulation of peripheral IL-1β-induced mechanical allodynia and thermal hyperalgesia in rats
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DOI：
10.1016/j.pain.2013.12.030
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发表时间：
2014-04-01
期刊：
影响因子：
7.4
通讯作者：
Ahn, Dong K.
中科院分区：
文献类型：
--
作者：
Kim, Min J.;Lee, Sang Y.;Ahn, Dong K.
本研究探讨了雄性Sprague-Dawley大鼠口面部注射白细胞介素（IL）1 β后，机械异常性疼痛和热痛觉过敏的差异机制。IL-1 β的皮下给药产生机械异常性疼痛和热痛觉过敏。虽然用瞬时受体电位香草酸1（TRPV 1）拮抗剂碘树脂毒素（IRTX）预处理不影响IL-1 β诱导的机械异常性疼痛，但其显著消除IL-1 β诱导的热痛觉过敏。另一方面，用N-甲基-D-天冬氨酸（NMDA）受体拮抗剂D-AP 5和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体拮抗剂NBQX预处理，可阻断IL-1 β诱导的机械性异常性疼痛。用蛋白激酶A（PKA）抑制剂H89预处理可阻断IL-1 β诱导的机械异常性疼痛，但不能阻断热痛觉过敏。与此相反，白屈菜红碱，蛋白激酶C（PKC）抑制剂，预处理抑制IL-1 β诱导的热痛觉过敏。皮下注射2%利多卡因（一种局部麻醉剂）可阻断IL-1 β诱导的热痛觉过敏，但不能阻断IL-1 β诱导的机械性异常性疼痛。在resiniferatoxin（RTX）预处理的大鼠，皮下注射IL-1 β并没有产生热痛觉过敏，由于在初级传入纤维的TRPV 1的耗竭。双重免疫荧光显示PKA与神经丝200（NF 200）和PKC与降钙素基因相关肽（CGRP）在三叉神经节的共定位。此外，NMDA受体1（NR 1）和TRPV 1主要共定位与PKA和PKC，分别在三叉神经节。这些结果表明，IL-1 β诱导的机械异常性疼痛是由致敏的外周NMDA/AMPA受体通过PKA介导的大直径初级传入神经纤维中的信号传导介导的，而IL-1 β诱导的热痛觉过敏是由致敏的外周TRPV 1受体通过PKC介导的小直径初级传入神经纤维中的信号传导介导的。(C)2014年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
This study examined the differential mechanisms of mechanical allodynia and thermal hyperalgesia after injection of interleukin (IL) 1 beta into the orofacial area of male Sprague-Dawley rats. The subcutaneous administration of IL-1 beta produced both mechanical allodynia and thermal hyperalgesia. Although a pre-treatment with iodoresiniferatoxin (IRTX), a transient receptor potential vanilloid 1 (TRPV1) antagonist, did not affect IL-1 beta-induced mechanical allodynia, it significantly abolished IL-1 beta-induced thermal hyperalgesia. On the other hand, a pretreatment with D-AP5, an N-methyl-D-aspartate (NMDA) receptor antagonist, and NBQX, an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, blocked IL-1 beta-induced mechanical allodynia. Pretreatment with H89, a protein kinase A (PKA) inhibitor, blocked IL-1 beta-induced mechanical allodynia but not thermal hyperalgesia. In contrast, pretreatment with chelerythrine, a protein kinase C (PKC) inhibitor, inhibited IL-1 beta-induced thermal hyperalgesia. Subcutaneous injections of 2% lidocaine, a local anesthetic agent, blocked IL-1 beta-induced thermal hyperalgesia but not IL-1 beta-induced mechanical allodynia. In the resiniferatoxin (RTX)-pretreated rats, a subcutaneous injection of IL-1 beta did not produce thermal hyperalgesia due to the depletion of TRPV1 in the primary afferent fibers. Double immunofluorescence revealed the colocalization of PKA with neurofilament 200 (NF200) and of PKC with the calcitonin gene-related peptide (CGRP) in the trigeminal ganglion. Furthermore, NMDA receptor 1 (NR1) and TRPV1 predominantly colocalize with PKA and PKC, respectively, in the trigeminal ganglion. These results suggest that IL-1 beta-induced mechanical allodynia is mediated by sensitized peripheral NMDA/AMPA receptors through PKA-mediated signaling in the large-diameter primary afferent nerve fibers, whereas IL-1 beta-induced thermal hyperalgesia is mediated by sensitized peripheral TRPV1 receptors through PKC-mediated signaling in the small-diameter primary afferent nerve fibers. (C) 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.