Jpn. J. Pharmacol. 75 (4), 327-335 (1997)

Nitric Oxide in the Rat Spinal Cord in Freund's Adjuvant-Induced Hyperalgesia

Norifumi Yonehara (1), Motohide Takemura (2), Masakazu Yoshimura (1), Katsuya Iwase (2), Han Geuk Seo (3), Naoyuki Taniguchi (3) and Yoshio Shigenaga (2)

Departments of (1) Pharmacology and (2) Oral Anatomy, Osaka University Faculty of Dentistry, 1-8 Yamadaoka, Suita, Osaka 565, Japan
(3) Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan

Abstract: 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.

Keywords: Nitric oxide synthase, Nicotinamide adenine dinucleotide phosphate-diaphorase, Nociception, Dorsal horn, Arthritis

Copyrightę The Japanese Pharmacological Society 1997

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