Yonehara N, Takemura M, Yoshimura M, Iwase K, Seo H G, Taniguchi N, Shigenaga Y
Department of Pharmacology, Osaka University Faculty of Dentistry, Suita, Japan.
Jpn J Pharmacol. 1997 Dec;75(4):327-35. doi: 10.1254/jjp.75.327.
To elucidate the involvement of nitric oxide in spinal nociceptive processing, the correlation of thermal withdrawal latency with nitric oxide synthase-stained neurons in the rat lumbar dorsal horn was analyzed after adjuvant-induced inflammation. From 4 hr through 5 days after subcutaneous injection of complete Freund's adjuvant into the hind paw, a marked thermal hyperalgesia was observed for heat stimulus applied to the affected region. NADPH-diaphorase- and nitric oxide synthase-positive neurons increased significantly in the superficial layers of the dorsal horn ipsilateral to the inflamed hind paw at day 3 of adjuvant-induced inflammation. No change in NADPH-diaphorase-positive neurons was observed at 1 hr and 1 day of adjuvant-induced inflammation. The intravenous administration of N omega-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg), an inhibitor of nitric oxide synthase, significantly blocked the adjuvant-induced thermal hyperalgesia at day 3 of inflammation, but not at day 1; and it had no effect in non-inflamed rats. This anti-hyperalgesic effect of L-NAME at day 3 of inflammation was reversed by the prior administration of L-arginine (600 mg/kg, i.p.), a substrate of nitric oxide synthase. These data suggest that nitric oxide producing neurons in the spinal dorsal horn are involved in maintaining and facilitating the hyperalgesia associated with chronic nociception.
为了阐明一氧化氮在脊髓伤害性信息处理中的作用，在佐剂诱导的炎症后，分析了大鼠腰段背角中热缩腿潜伏期与一氧化氮合酶染色神经元之间的相关性。在将完全弗氏佐剂皮下注射到后爪后4小时至5天内，观察到对施加于患区的热刺激有明显的热痛觉过敏。在佐剂诱导炎症的第3天，在同侧发炎后爪的背角浅层中，烟酰胺腺嘌呤二核苷酸磷酸黄递酶和一氧化氮合酶阳性神经元显著增加。在佐剂诱导炎症的1小时和1天时，未观察到烟酰胺腺嘌呤二核苷酸磷酸黄递酶阳性神经元有变化。静脉注射一氧化氮合酶抑制剂Nω-硝基-L-精氨酸甲酯（L-NAME，50mg/kg）在炎症第3天显著阻断了佐剂诱导的热痛觉过敏，但在第1天没有；并且在未发炎的大鼠中没有作用。在炎症第3天L-NAME的这种抗痛觉过敏作用被预先给予一氧化氮合酶的底物L-精氨酸（600mg/kg，腹腔注射）所逆转。这些数据表明，脊髓背角中产生一氧化氮的神经元参与维持和促进与慢性伤害感受相关的痛觉过敏。
