Blockade of joint inflammation and secondary hyperalgesia by L-NAME, a nitric oxide synthase inhibitor

ACUTE arthritis is associated with pain-related behavior, joint swelling and increased joint temperature. Arthritic animals exhibit a significant decrease in paw withdrawal latency 4, 5, 6, 7 and 8 h after induction of inflammation, when compared with baseline values, indicative of secondary hyperalgesia. Intra-articular injection of a non-specific nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester hydrochloride (L-NAME), resulted in a complete reversal of heat hyperalgesia and prevented further increase in joint swelling and temperature, while injection of either isotonic saline or the inactive enantiomer NG-nitro-D-arginine methyl ester (D-NAME) after induction of arthritis had no effect on any of these parameters. Intra-articular injection of 7-nitro-indazole (7-NINA), a selective neuronal NOS inhibitor, reversed the heat hyperalgesia for about Ih but did not inhibit the increase in joint swelling or temperature. These results suggest an important role for nitric oxide (NO) in mediating peripheral nociceptive transmission and inflammation.