Enhanced pronociception by amygdaloid group I metabotropic glutamate receptors in nerve-injured animals
Enhanced pronociception by amygdaloid group I metabotropic glutamate receptors in nerve-injured animals
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DOI：
10.1016/j.expneurol.2008.11.005
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发表时间：
2009-03-01
影响因子：
5.3
通讯作者：
Pertovaara, Antti
中科院分区：
文献类型：
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作者：
Ansah, Osei B.;Goncalves, Leonor;Pertovaara, Antti
周围神经病变与杏仁核的结构和功能变化有关，杏仁核是情绪的关键角色。在这里我们研究周围神经病变是否影响杏仁核对疼痛的调节。为此，我们在杏仁核中央核注射各种谷氨酸能化合物后，测定了扁桃体吻侧腹内侧髓质（RVM）中可能具有促痛觉性和抗痛觉性的疼痛调节神经元的放电率。周围神经损伤或假手术大鼠经戊巴比妥麻醉后，记录RVM神经元。在另一项单独的行为实验中，我们确定了杏仁核给药谷氨酸能化合物对情感性疼痛相关行为的影响（通过厌恶位置条件反射测试评估）是否会因神经病变而改变。虽然杏仁核中的谷氨酸或NMDA受体拮抗剂未能诱导RVM细胞放电率的显着变化，但在神经损伤而非假手术的动物中，杏仁核给药DHPG，一种作用于mGluR(1)和mGluR(5)的I组代谢型谷氨酸受体（mGluR）激动剂，增加了可能是前感觉性RVM on细胞的放电率。DHPG的这种预知作用被MPEP （mGluR(5)拮抗剂）和CPCCOEt （mGluR(1)拮抗剂）逆转。CHPG，一种mGluR(5)激动剂，不能影响on细胞的活性，DHPG不能影响可能具有抗感知能力的RVM off细胞的活性。在神经损伤动物中，给药DHPG增加杏仁核，CPCCOEt减少情感性疼痛相关行为。结果表明，神经损伤后，杏仁核蛋白I组mGluR，特别是mGluR(1)亚型，具有增强的前觉性作用，为周围神经病变疼痛的情绪增强提供了潜在的机制。(C) 2008爱思唯尔公司版权所有。
Peripheral neuropathy has been associated with structural and functional changes of the amygdala, a key player in emotions. Here we study whether peripheral neuropathy influences pain regulation by the amygdala. For this purpose, we determined discharge rates of presumably pro- and antinociceptive pain-regulatory neurons in the rostral ventromedial medulla (RVM) following microinjection of various glutamatergic compounds into the central nucleus of the amygdala. RVM neurons were recorded in pentobarbitone-anesthetized rats with a peripheral nerve injury or sham-operation. In a separate behavioral experiment, we determined whether the influence of amygdaloid administration of a glutamatergic compound on affective pain-related behavior, as assessed by an aversive place-conditioning test, is changed by neuropathy. While glutamate or an NMDA receptor antagonist in the amygdala failed to induce marked changes in discharge rates of RVM cells, amygdaloid administration of DHPG, a group I metabotropic glutamate receptor (mGluR) agonist acting on mGluR(1) and mGluR(5), increased discharge rates of presumably pronociceptive RVM ON-cells in nerve-injured but not sham-operated animals. This pronociceptive effect of DHPG was reversed by MPEP (mGluR(5) antagonist) and CPCCOEt (mGluR(1) antagonist). CHPG, an mGluR(5) agonist, failed to influence ON-cell activity and DHPG failed to influence activity of presumably antinociceptive RVM OFF-cells. Amygdaloid administration of DHPG increased and that of CPCCOEt decreased affective pain-related behavior in nerve-injured animals. The results suggest that following nerve injury, the amygdaloid group I mGluR, particularly subtype mGluR(1), has an enhanced pronociceptive effect providing a potential mechanism for emotional enhancement of pain in peripheral neuropathy. (C) 2008 Elsevier Inc. All rights reserved.