Activation of p38 MAPK in primary afferent neurons by noxious stimulation and its involvement in the development of thermal hyperalgesia
Activation of p38 MAPK in primary afferent neurons by noxious stimulation and its involvement in the development of thermal hyperalgesia
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DOI：
10.1016/j.pain.2004.09.038
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发表时间：
2005-01-01
期刊：
影响因子：
7.4
通讯作者：
Noguchi, K
中科院分区：
文献类型：
--
作者：
Mizushima, T;Obata, K;Noguchi, K
初级传入神经细胞内信号转导通路的改变可能导致疼痛超敏反应。我们证明，非常快速的磷酸化p38丝裂原活化蛋白激酶发生在背根神经节（DRG）的神经元参与传递有害信号。辣椒素注射后2 min，在小直径至中等直径的感觉神经元中诱导磷酸化p38（p-p38）。此外，我们研究了伤害性热刺激后背根神经节中的p-p38标记，发现标记细胞的大小和激活神经元的数量随刺激强度的增加而增加。这些p-p38免疫反应（IR）神经元大多数是小型和中型神经元，共表达瞬时受体电位离子通道TRPV 1和磷酸化细胞外信号调节蛋白激酶。鞘内给予p38抑制剂。FR 167653。逆转了辣椒素注射引起的热痛觉过敏。辣椒素注射后DRG中p-p38-IR神经元数量的减少证实了p38激活的抑制。加在一起。这些发现表明，在体内由伤害性刺激引起的初级传入中的p38通路的激活可能至少部分地与功能活动相关，并且进一步参与热痛觉过敏的发展。(C)2004年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
Alterations in the intracellular signal transduction pathway in primary afferents may contribute to pain hypersensitivity. We demostrated that very rapid phosphorylation of p38 mitogen-activated protein kinase occurred in dorsal root ganglion (DRG) neurons that were participating in the transmission of noxious signals. Capsaicin injection induced phosphorylated-p38 (p-p38) in small-to-medium diameter sensory neurons with a peak at 2 min after capsaicin injection. Furthermore, we examined the p-p38 labeling ill the DRG after noxious thermal stimuli and found a stimulus intensity-dependent increase in labeled cell size and the number of activated neurons. Most of these p-p38-immunoreactive (IR) neurons were small- and medium-sized neurons, which coexpressed transient receptor potential ion channel TRPV1 and phosphorylated-extracellular signal-regulated protein kinase. Intrathecal administration of the p38 inhibitor. FR 167653. reversed the thermal hyperalgesia produced by the capsaicin injection. Inhibition of p38 activation was confirmed by the decrease in the number of p-p38-IR neurons in the DRG following capsaicin injection. Taken together. these findings suggest that the activation of p38 pathways in primary afferents by noxious stimulation in vivo may be, at least in part, correlated with functional activity, and further, involved in the development of thermal hyperalgesia. (C) 2004 Intemational Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.