INVOLVEMENT OF NITRIC OXIDE IN MAINTAINING AND FACILITATING THE HYPERALGESIA ASSOCIATED WITH CHRONIC NOCICEPTION IN THE SITE OF THE FIRST SYNAPTIC RELAY OF THE PAIN PATHWAY

点击翻译按钮获取中文摘要

In order to elucidate the involvement of nitric oxide in spinal nociceptive processing, a correlation of thermal withdrawal latency with nitric oxide synthase-stained neurons in the rat lumbar dorsal horn was analyzed after adjuvant- or heat-induced inflammation. From 4 hrs through 5 days after subcutaneous injection of complete Freund's adjuvant into the hind paw, a marked thermal hyperalgesia was observed following heat stimulus applied to the affected region. In control rats, NADPH-diaphorase-positive neurons were observed in laminae I through V with a higher density at the border between laminae II and III in the lumbar spinal dorsal horn, and they were also stained immunohistochemically for rat cerebellar nitric oxide synthase. NADPH-diaphorase- and nitric oxide synthase-positive neurons increased significantly in the superficial layrs of the dorsal horn ipsilateral to the inflamend 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, or at 1 hr, 1 and 3 days of heat-induced inflammation (47ﾟC for 30 min). The intravenous administration of N^<omega>-L-arginine methyl ester (LNAME,50 mg/kg), an antagonist of nitric oxide synthase, significantly blocked the adjuvant-induced thermal hyperalgesia at day 3 of inflammation, but not at day 1, and had no effect in non-inflamed rats. This anti-hyperalgesic effect of LNAME at day 3 of inflammation was reversed by the priodministration of L-arginine (500 mg/kg i.p.), a substrate of nitric oxide synthase.These data suggest that nitric oxide producing neurons in the site of the first synaptic relay of the pain pathway are involved in maintaining and facilitating the hyperalgesia associated with chronic nociception.