Dual effect of nitric oxide in articular inflammatory pain in zymosan‐induced arthritis in rats

Abstract

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 μmol; 1400W, 0.01 (μmol) 30 min before zymosan also inhibited the AI. Systemic or local treatment with the NOS inhibibitors (L‐NAME; AG, 100 mg kg−1 i.p. or 0.1 μmol joint−1; 1400W, 1 mg kg−1 s.c. or 0.01 μmol 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 E2 (PGE2) 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 PGE2 release or oedema. NO donors also promoted antinociception in zymosan arthritis without affecting oedema. British Journal of Pharmacology (2002) 136, 588–596; doi:

Role of nitric oxide in the local and systemic pathophysiological effects induced by Bothrops asper snake venom in mice

“…A reduction in infl ammatory infi ltrate, associated with reduced L-selectin expression, was described as a consequence of L-NAME treatment in a model of B. jararaca venom-induced infl ammation in rats [46]. Hence, despite confl icting fi ndings on the role of NO in infl ammatory phenomena (see for example [47] and [48]), which may depend on the use of different NOS inhibition protocols and differences in the microvasculature of various tissues, our fi ndings and those of others suggest that NO promotes various aspects of infl ammation in models involving Bothrops sp venom injection. The lack of effect of NOS inhibition in the infl ammatory infi ltrate at 24 and 48 h suggests that infl ammatory mediators other than NO play a predominant role in leucocyte recruitment at these earlier time intervals.…”

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

“…The mechanical hyperalgesia in zymosan-induced arthritis in rats was reduced by local (intraarticular) pretreatment with nonselective or iNOS-selective inhibitors before zymosan injection; however, these drugs were without effect if they were given after development of arthritis (609). As NO donors given locally after development of arthritis inhibited mechanical hyperalgesia without affecting edema, pointing to an antinociceptive effect of NO, the authors ascribed the former effect to inhibition of synovial inflammation by reduced formation of the proinflammatory NO.…”

Dual effect of nitric oxide donor on adjuvant arthritis

“…Furthermore, Kim et al reported that SNP in low concentrations protects chondrocytes from toxic effect of the higher concentration [39]. Consistent with the notion of a dual effects of NO donors, several experiments have shown that local application of drugs generating a low NO concentration reduces incision pain through activation of guanylate cyclase while drugs generating high NO concentration intensify pain via guanylate cyclase-independent mechanism [47,48]. With respect to joint pain there is only one clinical study showing that transdermal nitroglycerin provided partial symptomatic pain relief in patient with painful shoulders [49].…”