Anterior cingulate cortex modulates visceral pain as measured by visceromotor responses in viscerally hypersensitive rats
Anterior cingulate cortex modulates visceral pain as measured by visceromotor responses in viscerally hypersensitive rats
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DOI：
10.1053/j.gastro.2007.11.057
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发表时间：
2008-02-01
期刊：
影响因子：
29.4
通讯作者：
Li, Ying
中科院分区：
文献类型：
--
作者：
Cao, Zhijun;Wu, Xiaoyin;Li, Ying
背景与目的：我们已发现扣带回前部神经元对大肠扩张(CRD)有反应，并发现内脏高敏感大鼠对ACC神经元有敏化作用。然而，ACC在疼痛反应中的作用还没有明确的定义。我们的目的是确定ACC神经元的激活是否会增强内脏高敏感大鼠的内脏疼痛，并确定参与内脏疼痛易化的受体。方法：采用正常大鼠和结肠过敏大鼠，记录CRD的伤害性反应(内脏运动反应VMR)。对ACC进行电刺激，并用鹅膏油酸产生ACC损伤。将L-谷氨酸、α-氨基-3-羟基-5-甲基-异氧唑丙酸受体拮抗剂氰基-喹恶啉二酮和N-甲基-D-天冬氨酸受体拮抗剂氨基膦戊酸微量注射到前交叉韧带吻部。结果：电刺激大鼠头端ACC可增强正常大鼠对CRD的VMR反应。损毁ACC可降低内脏高敏感大鼠的VMR，但对正常大鼠无影响。在内脏高敏感大鼠中，微量注射2 mm ol/L谷氨酸可增加内脏高敏感大鼠对慢性阻塞性肺疾病(10 Mm Hg)的VMR，而20 mm ol/L谷氨酸可使内脏高敏感大鼠的VMR增加。氰基喹恶啉二酮对两组的VMR均无影响。氨基膦戊酸可显著抑制内脏高敏感大鼠的VMR，但对正常大鼠无明显影响。结论：ACC在内脏高敏感大鼠内脏痛反应的调节中起重要作用。这一过程似乎是由谷氨酸N-甲基-D-天冬氨酸受体活性增强所介导的。
Background & Aims: We have identified that the anterior cingulate cortex (ACC) neurons are responsive to colorectal distention (CRD) and shown that sensitization of ACC neurons occurs in viscerally hypersensitive rats. However, the role of the ACC in pain response has not been clearly defined. We aimed to determine if ACC neuron activation enhances visceral pain in viscerally hypersensitive rats and to identify the receptor involved in facilitation of visceral pain. Methods: The nociceptive response (visceromotor response [VMR]) to CRD was recorded in normal and viscerally hypersensitive rats induced by colonic anaphylaxis. The ACC was stimulated electrically, and ACC lesions were generated with ibotenic acid. L-glutamate, alpha-amino-3-hydroxy-5-methyl-isoxozole propionic acid receptor antagonist cyanonitroquinoxaline dione, and N-methyl-D-aspartate receptor antagonist aminophosphonopentanoic acid were microinjected into the rostral ACC. Results: Electrical stimulation of the rostral ACC enhanced the VMR to CRD in normal rats. ACC lesions caused a decrease in the VMR in viscerally hypersensitive rats but had no effect in normal rats. ACC microinjection of 2 mmol/L glutamate increased the VMR to CRD (10 mm Hg) in viscerally hypersensitive rats, and 20 mmol/L glutamate induced a more potent VMR in viscerally hypersensitive than in normal rats. Cyanonitroquinoxaline dione did not affect the VMR in either group. Aminophosphonopentanoic acid significantly suppressed the VMR in viscerally hypersensitive rats but not in normal rats. Conclusions: The ACC plays a critical role in the modulation of visceral pain responses in viscerally hypersensitive rats. This process appears to be mediated by enhanced activities of glutamate N-methyl-D-aspartate receptors.