Biphasic Activation of Extracellular Signal-regulated Kinase in Anterior Cingulate Cortex Distinctly Regulates the Development of Pain-related Anxiety and Mechanical Hypersensitivity in Rats after Incision
Biphasic Activation of Extracellular Signal-regulated Kinase in Anterior Cingulate Cortex Distinctly Regulates the Development of Pain-related Anxiety and Mechanical Hypersensitivity in Rats after Incision
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前扣带皮层细胞外信号调节激酶的双相激活明显调节大鼠切口后疼痛相关焦虑和机械超敏反应的发展
DOI：
10.1097/aln.0b013e3182242045
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发表时间：
2011-09-01
期刊：
影响因子：
8.8
通讯作者：
Zhou, Xin-Fu
中科院分区：
文献类型：
--
作者：
Dai, Ru-Ping;Li, Chang-Qi;Zhou, Xin-Fu
背景资料：最近的一项研究表明，手术切口诱导焦虑样行为，但其与切口诱发的机械超敏反应的关系仍然难以捉摸。前扣带皮层（ACC）细胞外信号调节激酶（ERK）活性在情感性疼痛中起重要作用。本研究旨在探讨ACC中ERK 1/2活性及其在切口后焦虑和机械性超敏反应发生中的作用。方法：采用高架十字迷宫实验和大鼠后足切开后旷场实验检测大鼠的类迷宫行为。免疫组化和Western blot检测ERK 1/2磷酸化。将套管植入双侧ACC中，用于ACC内注射ERK抑制剂PD 98059和U 0126。在切口疼痛条件下，采用刷牙（无害刺激）来研究其对ERK激活的影响。结果：由后爪切口引起的焦虑样行为持续时间长于机械性超敏反应。一个后爪切口导致双相ERK激活在双侧ACC。抑制ERK激活在早期衰减疼痛相关的焦虑和机械过敏，而抑制ERK激活在晚期只减少焦虑样行为。在ERK激活的两个阶段之间的时间间隔期间，刷洗切开的皮肤显著增加ACC中的ERK磷酸化。这些数据表明，在术后疼痛的早期阶段，疼痛相关的焦虑和机械超敏反应是紧密联系在一起的，并受到ACC中ERK激活的调节。ACC中ERK的激活仅是疼痛相关焦虑的表达所需，而不是机械超敏反应。
Background: A recent study has demonstrated that surgical incision induces an anxiety-like behavior but its relationship with incision-evoked mechanical hypersensitivity remains elusive. Extracellular signal-regulated kinase (ERK) activity in the anterior cingulate cortex (ACC) is important for the affective pain. The current study aims to explore ERK1/2 activity in the ACC and its role in the development of anxiety and mechanical hypersensitivity after incision. Methods: Anxiety-like behavior was measured by elevated plus maze experiment and open field test after hind paw incision. ERK1/2 phosphorylation was determined by immunohistochemistry and Western blot. Cannulae were implanted into the bilateral ACC for the intra-ACC injection of ERK inhibitors PD98059 and U0126. Brushing (innocuous stimulus) was used to investigate its effect on ERK activation under the incision-evoked painful condition. Results: The anxiety-like behavior induced by the hind paw incision persisted longer than mechanical hypersensitivity. One hind paw incision resulted in a biphasic ERK activation in bilateral ACC. Inhibiting ERK activation in the early phase attenuated pain-related anxiety and mechanical hypersensitivity whereas inhibiting ERK activation in the late phase only reduced the anxiety-like behavior. During the time interval between two phases of ERK activation, brushing the incised skin dramatically increased ERK phosphorylation in the ACC. Conclusions: These data suggest that in the early phase of postoperative pain, pain-related anxiety and mechanical hypersensitivity are tightly linked and regulated by the ERK activation in the ACC. However, in the late phase of postoperative pain, ERK activation in the ACC is only required for the expression of pain-related anxiety but not mechanical hypersensitivity.