Coutinho V S, Urban O M, Gebhart F G
Department of Pharmacology, Bowen Science Building, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
Pain. 1998 Oct;78(1):59-69. doi: 10.1016/S0304-3959(98)00137-7.
The present study was undertaken to examine the involvement of descending pain modulatory systems from the brainstem rostral ventromedial medulla (RVM) in modulating visceral hyperalgesia produced by intracolonic instillation of zymosan. Three hours after intracolonic zymosan, the visceromotor response (VMR) to noxious colorectal distension (CRD, 80 mmHg, 20s) was increased significantly. This hyperalgesia was attenuated in a dose-dependent manner by the selective NMDA receptor antagonist APV (10-30 fmol, 1 microl) microinjected into the RVM. The hyperalgesia was also attenuated by intra-RVM administration of the nitric oxide synthase (NOS) inhibitor L-NAME. In support, there was a significant increase in the number of cells in the RVM labeled for NADPH diaphorase (NADPH-d) or neuronal NOS (nNOS) in zymosan-treated rats. In contrast to the effects of APV and L-NAME, administration of the non-NMDA receptor antagonist DNQX into the RVM further enhanced the already facilitated VMR to CRD in zymosan-treated rats. Taken together, these data suggest that zymosan-produced visceral hyperalgesia is influenced by two descending pain modulatory systems: a facilitatory system mediated by activation of NMDA receptors in the RVM and production of nitric oxide, and an inhibitory system mediated by activity at non-NMDA receptors in the RVM. The unmasking of one system by selective blockade of the other suggests simultaneous activation of both by colonic inflammation.
本研究旨在探讨来自脑干头端腹内侧延髓（RVM）的下行性疼痛调制系统在调节结肠内注入酵母聚糖所产生的内脏痛觉过敏中的作用。结肠内注入酵母聚糖3小时后，对有害性结肠扩张（CRD，80 mmHg，20秒）的内脏运动反应（VMR）显著增加。将选择性NMDA受体拮抗剂APV（10 - 30 fmol，1微升）微量注射到RVM中，这种痛觉过敏以剂量依赖性方式减弱。RVM内给予一氧化氮合酶（NOS）抑制剂L - NAME也可减弱痛觉过敏。此外，酵母聚糖处理的大鼠中，RVM内标记为还原型辅酶II黄递酶（NADPH - d）或神经元型NOS（nNOS）的细胞数量显著增加。与APV和L - NAME的作用相反，将非NMDA受体拮抗剂DNQX注入RVM会进一步增强酵母聚糖处理的大鼠中已经增强的对CRD的VMR。综上所述，这些数据表明酵母聚糖产生的内脏痛觉过敏受两个下行性疼痛调制系统影响：一个是由RVM中NMDA受体激活和一氧化氮产生介导的易化系统，另一个是由RVM中非NMDA受体活性介导的抑制系统。通过选择性阻断另一个系统来揭示一个系统，这表明结肠炎症同时激活了这两个系统。
