Inhibition of p38 mitogen-activated protein kinase activation in the rostral anterior cingulate cortex attenuates pain-related negative emotion in rats
Inhibition of p38 mitogen-activated protein kinase activation in the rostral anterior cingulate cortex attenuates pain-related negative emotion in rats
复制标题
抑制大鼠前扣带皮层 p38 丝裂原激活蛋白激酶的激活可减轻疼痛相关的负面情绪
DOI：
10.1016/j.brainresbull.2014.06.005
复制
发表时间：
2014-08-01
影响因子：
3.8
通讯作者：
Zhang, Yu-Qiu
中科院分区：
文献类型：
--
作者：
Cao, Hong;Zang, Kai-Kai;Zhang, Yu-Qiu
对疼痛的情绪成分的研究远少于对感觉成分的研究。先前的研究表明，头侧前扣带皮层（rACC）与对有害刺激的情感反应有关。脊髓中 p38 丝裂原激活蛋白激酶 (MAPK) 的激活已被证明在多种病理疼痛状态中发挥重要作用。我们在大鼠中使用福尔马林诱导的条件性地方厌恶 (F-CPA)（一种被认为反映对疼痛的情绪反应的动物模型）来研究诱导情感性疼痛后 p38 MAPK 在 rACC 中的参与情况。足底内注射福尔马林可显着激活双侧 rACC 中的 p38 MAPK 及其上游激活剂丝裂原激活激酶激酶 (MKK) 3 和 MKK6。 rACC 中 NeuN 阳性神经元和 Iba1 阳性小胶质细胞中的 p38 MAPK 升高，但 GFAP 阳性细胞中则没有升高。使用其特异性抑制剂 SB203580 或 SB239063 阻断双侧 rACC 中 p38 MAPK 的激活，剂量依赖性地抑制 F-CPA 的形成。抑制 p38 MAPK 激活不影响福尔马林诱导的两相自发伤害性反应和低强度电足电击诱导的 CPA。本研究表明 rACC 中的 p38 MAPK 信号通路有助于与疼痛相关的负面情绪。因此，针对 p38 MAPK 级联的新药理学策略可能有助于治疗与疼痛相关的情绪障碍。 (C) 2014 Elsevier Inc. 保留所有权利。
The emotional components of pain are far less studied than the sensory components. Previous studies have indicated that the rostral anterior cingulate cortex (rACC) is implicated in the affective response to noxious stimuli. Activation of p38 mitogen-activated protein kinase (MAPK) in the spinal cord has been documented to play an important role in diverse kinds of pathological pain states. We used formalin-induced conditioned place aversion (F-CPA) in rats, an animal model believed to reflect the emotional response to pain, to investigate the involvement of p38 MAPK in the rACC after the induction of affective pain. Intraplantar formalin injection produced a significant activation of p38 MAPK, as well as mitogen-activated kinase kinase (MKK) 3 and MKK6, its upstream activators, in the bilateral rACC. p38 MAPK was elevated in both NeuN-positive neurons and Iba1-positive microglia in the rACC, but not GFAP-positive cells. Blocking p38 MAPK activation in the bilateral rACC using its specific inhibitor SB203580 or SB239063 dose-dependently suppressed the formation of F-CPA. Inhibiting p38 MAPK activation did not affect formalin-induced two-phase spontaneous nociceptive response and low intensity electric foot-shock induced CPA. The present study demonstrated that p38 MAPK signaling pathway in the rACC contributes to pain-related negative emotion. Thus, a new pharmacological strategy targeted at the p38 MAPK cascade may be useful in treating pain-related emotional disorders. (C) 2014 Elsevier Inc. All rights reserved.