Lin Q, Palecek J, Palecková V, Peng Y B, Wu J, Cui M, Willis W D
Department of Anatomy and Neurosciences, Marine Biomedical Institute, The University of Texas Medical Branch, Galveston, Texas 77555-1069, USA.
J Neurophysiol. 1999 Mar;81(3):1075-85. doi: 10.1152/jn.1999.81.3.1075.
Nitric oxide (NO) has been proposed to contribute to the development of hyperalgesia by activating the NO/guanosine 3',5'-cyclic monophosphate (cGMP) signal transduction pathway in the spinal cord. We have examined the effects of NO on the responses of primate spinothalamic tract (STT) neurons to peripheral cutaneous stimuli and on the sensitization of STT cells following intradermal injection of capsaicin. The NO level within the spinal dorsal horn was increased by microdialysis of a NO donor, 3-morpholinosydnonimine (SIN-1). SIN-1 enhanced the responses of STT cells to both weak and strong mechanical stimulation of the skin. This effect was preferentially on deep wide dynamic range STT neurons. The responses of none of the neurons tested to noxious heat stimuli were significantly changed when SIN-1 was administered. Intradermal injection of capsaicin increased dramatically the content of NO metabolites, NO-2/NO-3, within the dorsal horn. This effect was attenuated by pretreatment of the spinal cord with a nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). Sensitization of STT cells induced by intradermal injection of capsaicin was also prevented by pretreatment of the dorsal horn with the NOS inhibitors, L-NAME or 7-nitroindazole. Blockade of NOS did not significantly affect the responses of STT cells to peripheral stimulation in the absence of capsaicin injection. The data suggest that NO contributes to the development and maintenance of central sensitization of STT cells and the resultant mechanical hyperalgesia and allodynia after peripheral tissue damage or inflammation. NO seems to play little role in signaling peripheral stimuli under physiological conditions.
一氧化氮（NO）被认为可通过激活脊髓中的NO/鸟苷3'，5'-环磷酸（cGMP）信号转导通路来促进痛觉过敏的发展。我们研究了NO对灵长类动物脊髓丘脑束（STT）神经元对外周皮肤刺激的反应以及皮内注射辣椒素后STT细胞敏化的影响。通过对NO供体3-吗啉代辛二亚胺（SIN-1）进行微透析，可增加脊髓背角内的NO水平。SIN-1增强了STT细胞对皮肤弱刺激和强机械刺激的反应。这种作用优先作用于深部广动力范围的STT神经元。给予SIN-1时，所测试的神经元对有害热刺激的反应均未发生显著变化。皮内注射辣椒素可显著增加背角内NO代谢产物NO-2/NO-3的含量。一氧化氮合酶（NOS）抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）预处理脊髓可减弱这种作用。用NOS抑制剂L-NAME或7-硝基吲唑预处理背角也可防止皮内注射辣椒素诱导的STT细胞敏化。在未注射辣椒素的情况下，阻断NOS对STT细胞对外周刺激的反应没有显著影响。数据表明，NO在周围组织损伤或炎症后STT细胞的中枢敏化以及由此产生的机械性痛觉过敏和异常性疼痛的发展和维持中起作用。在生理条件下，NO似乎在传导外周刺激信号方面作用不大。
