NMDA受体NR2B亚单位在慢性内脏痛觉敏化中的作用

Effect of NMDA receptors NR2B subunit on chronic visceral hypersensitivity

目的探讨外周与脊髓NMDA受体NR2B亚单位在慢性内脏痛觉敏化中的作用。方法模型组大鼠出生后d8～15,每天接受一次伤害性结直肠扩张刺激,8wk龄后用腹壁撤退反射(AWR)评估大鼠肠道敏感性。对腰骶背根神经节及胸腰与腰骶脊髓背角神经元进行免疫组织化学染色,比较对照与模型大鼠NR2B的表达。并比较对照与模型两组大鼠腹腔注射AP-7(NMDA受体拮抗剂)前后原发传入神经对结直肠扩张刺激的反应。结果①模型组大鼠AWR评分显著增高。②模型大鼠脊髓背根神经节NR2B亚单位表达增强。③模型大鼠脊髓内脏相关神经元NR2B亚单位表达增强。④AP-7显著抑制模型大鼠腰骶传入神经纤维对结直肠刺激的反应。结论NMDA受体NR2B亚单位可能参与慢性内脏痛外周与脊髓痛觉敏化的过程。

Aim To explore effects of peripheral and spinal NMDA receptor NR2B subunit on chronic visceral hypersensitivity. Methods Model rats received daily noxious colorectal distensions （CRD） on postna- tal days 8 - 15. Visceral hypersensitivity of rats were e- valuated by abdominal withdrawal reflex （AWR） when they were 8 weeks old. Expression of NMDA receptor NR2B subunit in dorsal root ganglions and spinal visceral related neurons was compared between control and model rats by immunohistochemistry method. Responses of primary afferents to CRD were compared before and after systemic administration of AP-7, a NM- DA antagonist, in control and model rats. Results （1） AWR scores significantly increased in adult model rats. （2） Image analysis showed that average optical density which represents the expression of NR2B sub- unit in dorsal root gangalia（DRG） was significantly in- creased in model rats than that in control rats. （3） analysis shows that average optical density which Image repre- sents the expression of NR2B subunit in spinal visceral related neurons was significantly higher in model rats than those in control rats （4） The percent inhibition of the responses of lunbosacral dorsal root to CRD caused by AP-7 was significantly higher in model rats than those in control rats. Conclusion NR2B may play a role in the peripheral and spinal mechanism of chronic visceral pain.