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 1 h 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.
Lawand
N B
NB
Marine Biomedical Institute, Department of Anatomy and Neuroscience, University of Texas Medical Branch at Galveston 77555-1069, USA.
Willis
W D
WD
Westlund
K N
KN
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001168:Arthritis / Q000503:physiopathology*; D002351:Carrageenan; D006930:Hyperalgesia / Q000503:physiopathology*; D007191:Indazoles / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000503:physiopathology*; D007270:Injections, Intra-Articular; D007536:Isomerism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
D000700:Analgesics; D007191:Indazoles; D002351:Carrageenan; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester