Dual effect of nitric oxide in articular inflammatory pain in zymosan-induced arthritis in rats.
The contribution of nitric oxide (NO) to articular pain in arthritis induced by zymosan (1 mg, intra articular) in rats was assessed by measuring articular incapacitation (AI). Systemic treatment with the non-selective NO synthase (NOS) inhibitor L-NAME (10 - 100 mg kg(-1) i.p.) or with the selective iNOS inhibitors aminoguanidine (AG; 10 - 100 mg kg(-1) i.p.) or 1400W (0.5 - 1 mg kg(-1) s.c.) inhibited the AI induced by injection of zymosan 30 min later. Local (intra articular) treatment with the NOS inhibitors (L-NAME or AG, 0.1 - 1 micromol; 1400W, 0.01 (micromol) 30 min before zymosan also inhibited the AI. Systemic or local treatment with the NOS inhibitors (L-NAME; AG, 100 mg kg(-1) i.p. or 0.1 micromol joint(-1); 1400W, 1 mg kg(-1) s.c. or 0.01 micromol joint(-1)), 2 h after zymosan did not affect the subsequent AI. Local treatment with the NO donors SNP or SIN-1, 2 h after zymosan did inhibit AI. L-NAME and AG, given i.p. inhibited nitrite but not prostaglandin E(2) (PGE(2)) levels in the joints. L-NAME (100 mg kg(-1)) but not AG (100 mg kg(-1)) increased mean arterial blood pressure. Neither L-NAME, AG nor the NO donor SIN-1 altered articular oedema induced by zymosan. In conclusion, inhibitors of iNOS decrease pain in zymosan arthritis only when given before the zymosan. This was not due to inhibition of articular PGE(2) release or oedema. NO donors also promoted antinociception in zymosan arthritis without affecting oedema.
da S  Rocha
José C
JC
Faculdade de Medicina - Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Rua Cel. Nunes de Melo, 1127 - CEP 60430-270, Fortaleza - Ceará - Brasil.
Peixoto
Magno E B
ME
Jancar
Sônia
S
de Q  Cunha
Fernando
F
de A  Ribeiro
Ronaldo
R
da Rocha
Francisco A C
FA
D000578:Amidines / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D001596:Benzylamines / Q000008:administration & dosage / Q000494:pharmacology; D002358:Cartilage, Articular / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology; D007270:Injections, Intra-Articular; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D015054:Zymosan
D000578:Amidines; D001596:Benzylamines; D004791:Enzyme Inhibitors; D006146:Guanidines; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D015054:Zymosan; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester