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 mu l of saline: no drug (control) (n = 13), 15 mu g of NOC-18 (n = 15); 150 mu g of NOC-18 (n = 9); 100 mu g of N-nitro-L-arginine methyl ester (L-NAME) (n = 8); 15 mu g of NOC-18 + 100 mu g of L-NAME (n = 8); 10 mu g of methylene blue (MB) (n = 8); 15 mu g of NOC-18 + 10 mu g of MB (n = 8). NOC-18 caused a dose-dependent curtailment (7% and 23% decreases for 15 mu g and 150 pig 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 pg of NOC-18. These findings indicate that the NO-cGMP pathway is directly involved in thermal hyperalgesia in the brain.