Intracerebroventricular administration of a nitric oxide-releasing compound, NOC-18, produces thermal hyperalgesia in rats.
This study was undertaken to define the role of nitric oxide (NO) in central nociceptive mechanisms by intracerebroventricular injection of an NO-releasing compound, NOC-18, in rats. The nociceptive threshold was evaluated by the radiant heat tail-flick test. Sixty-nine rats were divided into the seven groups, and the following drugs were injected intracerebroventricularly in 5 microliters of saline: no drug (control) (n = 13), 15 micrograms of NOC-18 (n = 15); 150 micrograms of NOC-18 (n = 9); 100 micrograms of N-nitro-L-arginine methyl ester (L-NAME) (n = 8); 15 micrograms of NOC-18 + 100 micrograms of L-NAME (n = 8); 10 micrograms of methylene blue (MB) (n = 8); 15 micrograms of NOC-18 + 10 micrograms of MB (n = 8). NOC-18 caused a dose-dependent curtailment (7% and 23% decreases for 15 micrograms and 150 micrograms of NOC-18, respectively) of the tail-flick latency during the period from 15 to 120 min. L-NAME caused prolongation (15% maximum) of the tail-flick latency during the period from 15 to 150 min. However, NOC-18-induced hyperalgesia was not influenced by L-NAME. MB also caused prolongation (9% maximum) of the tail-flick latency during the period from 15 to 150 min, and completely blocked the hyperalgesia induced by 15 micrograms of NOC-18. These findings indicate that the NO-cGMP pathway is directly involved in thermal hyperalgesia in the brain.
Shibuta
S
S
Department of Anesthesiology, Osaka University Medical School, Japan.
Mashimoto
T
T
Ohara
A
A
Zhang
P
P
Yoshiya
I
I
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects*; D001921:Brain / Q000502:physiology*; D006930:Hyperalgesia / Q000139:chemically induced*; D007276:Injections, Intraventricular; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009603:Nitroso Compounds / Q000008:administration & dosage*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
C093285:NOC 18; D009603:Nitroso Compounds; D009569:Nitric Oxide; D001120:Arginine; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester