阻断炎症局部5-HT2A受体对大鼠脊髓背角一氧化氮合酶表达的影响

EFFECTS OF BLOCKADE OF 5-HT_(2A) RECEPTORS IN THE INFLAMMATORY TISSUES ON THE EXPRESSION OF NITRIC OXIDE SYNTHASE IN THE SPINAL CORD OF RATS

目的:研究阻断局部炎症组织中的5-HT2A受体后,脊髓背角一氧化氮合酶的变化,以了解外周5-HT2A受体在慢性炎症维持中的作用。方法:给大鼠足掌皮下注射2%角叉菜胶(carrageenan),1h后注射5-HT2A受体拮抗剂酮舍林(ketanserin)20μg。24h于大鼠同一位点注射1%福尔马林(formalin)。25h灌流、取材,进行NADPH-d组织化学实验。结果:注射角叉菜胶和福尔马林后,双侧脊髓背角浅层的NADPH-d阳性神经元数目均增多,以同侧更为显著。给予酮舍林后明显抑制这种增加。外周阿片受体拮抗剂纳洛酮(naloxone methiodide)可使酮舍林对炎症引起NADPH-d阳性神经元的抑制作用完全消失。结论:阻断外周5-HT2A受体能抑制角叉菜胶和福尔马林炎性痛刺激引起脊髓背角神经元的活化,这种抑制作用可能是通过激活阿片镇痛机制,继而抑制一氧化氮信号通路实现的。

Objective： To investigate the expression of nitric oxide synthase in the spinal cord following the blockade of 5-HT2A receptors of inflammatory tissues. Methods： 2% carrageenan was injected subcutaneously into one hindpaw of rats. Vehicle or ketanserin 20 μg and 1% formalin were injected at 1 and 24 h, respectively, after carrageenan in the same site. The rats were perfused at 25 h. The NADPH-diaphorase histochemistry in the spinal cord was determined. Results： Compared to the vehicle treatment, intraplantar injection of 1% formalin in the inflammatory paw produced remarkable increase in NADPH-d reactive neurons that were predominantly distributed in laminae Ⅰ-Ⅱ of spinal dorsal horn at L4 - L5 segments. The increase was abolished by ketanserin. Interestingly, inhibition of ketanserin on inflammationevoked increase of NADPH reactivity was reversed by subcutaneous administration of naloxone methiodide, a peripheral opioid receptor antagonist. Conclusion： Peripheral 5-HT plays an important role in the maintenance of inflammatory hyperalgesia, and that blockade of 5-HT2A receptor could activate endogenous opioid analgesia leading to an increase in nitric oxide synthase.