NMDA NR2A and NR2B receptors in the rostral anterior cingulate cortex contribute to pain-related aversion in male rats.

NMDA NR2A and NR2B receptors in the rostral anterior cingulate cortex contribute to pain-related aversion in male rats.
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头侧前扣带皮层中的 NMDA NR2A 和 NR2B 受体有助于雄性大鼠与疼痛相关的厌恶。

DOI:
10.1016/j.pain.2009.07.027
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发表时间:
2009-11
期刊:
影响因子:
7.4
通讯作者:
Zhang YQ
Zhang YQ
中科院分区:
医学1区
文献类型:
--
作者:
Li TT;Ren WH;Xiao X;Nan J;Cheng LZ;Zhang XH;Zhao ZQ;Zhang YQ

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与疼痛处理有关的NMDA受体在包括前扣带皮层(ACC)在内的前脑区域高度表达。ACC参与了对伤害性刺激的情感反应。本研究采用免疫组织化学染色、western blot、电生理记录和福尔马林诱导的条件性位置回避(F-CPA)大鼠行为模型相结合的方法,研究福尔马林伤害性条件刺激引起的大鼠前扣带(rACC)NMDA受体亚单位NR 1、NR 2A和NR 2B表达的变化及其可能的功能意义。我们发现,单侧足底内(i.pl.)注射稀释福尔马林后,无论是否有条件暴露,均显著增加双侧rACC中NMDA受体亚单位NR 2A和NR 2B的表达,但对NR 1的表达无影响。注射福尔马林的大鼠rACC神经元的NMDA诱发电流显著大于未注射或注射生理盐水的大鼠。选择性阻断rACC中NR 2A或NR 2B亚基可阻断F-CPA的获得和福尔马林伤害性条件刺激诱导的Fos表达,但不影响福尔马林急性伤害性行为和非伤害性恐惧刺激诱导的CPA。这些结果表明,NMDA受体亚单位NR 2A和NR 2B在rACC是至关重要的参与疼痛相关的厌恶。因此,针对NMDA受体NR 2A或NR 2B亚基可能成为预防疼痛相关情绪障碍的新策略。
NMDA receptors, which are implicated in pain processing, are highly expressed in forebrain areas including the anterior cingulate cortex (ACC). The ACC has been implicated in the affective response to noxious stimuli. Using a combination of immunohistochemical staining, western blot, electrophysiological recording and formalin-induced conditioned place avoidance (F-CPA) rat behavioral model that directly reflects the affective component of pain, the present study examined formalin nociceptive conditioning-induced changes in the expressions of NMDA receptor subunits NR1, NR2A, and NR2B in the rostral ACC (rACC) and its possible functional significance. We found that unilateral intraplantar (i.pl.) injection of dilute formalin with or without contextual conditioning exposure markedly increased the expressions of NMDA receptor subunits NR2A and NR2B but not NR1 in the bilateral rACC. NMDA-evoked currents in rACC neurons were significant greater in formalin-injected rats than that of naïve or normal saline-injected rats. Selectively blocking either NR2A or NR2B subunit in the rACC abolished the acquisition of F-CPA and formalin nociceptive conditioning-induced Fos expression, but did not affect formalin acute nociceptive behaviors and non-nociceptive fear stimulus-induced CPA. These results suggest that both NMDA receptor subunits NR2A and NR2B in the rACC are critically involved in pain-related aversion. Thus, a new strategy targeted at NMDA NR2A or NR2B subunit might be raised for the prevention of pain-related emotional disturbance.
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