We investigated the effect of an extract from a helminth (Ascaris suum) in zymosan-induced arthritis (ZYA) or collagen-induced arthritis (CIA). Rats and mice, respectively, received 1 mg and 0.1 mg zymosan intraarticularly (i.a.). Test groups received an A. suum extract either per os (p.o.) or intraperitoneally (i.p.) 30 min prior to i.a. zymosan. Controls received saline. Hypernociception was measured using the articular incapacitation test. Cell influx, nitrite, and cytokine levels were assessed in joint exudates. The synovia and distal femoral extremities were used for histopathology. Cartilage damage was assessed through determining glycosaminoglycan (GAG) content. DBA/1J mice were subjected to CIA. The test group received A. suum extract i.p. 1 day after CIA became clinically detectable. Clinical severity and hypernociception were assessed daily. Neutrophil influx was determined using myeloperoxidase activity. The A. suum extract, either i.p. or p.o., significantly and dose-dependently inhibited cell influx and hypernociception in ZYA in addition to reducing GAG loss and ameliorating synovitis. The A. suum extract reduced i.a. levels of NO, interleukin-1␤ (IL-1␤), and IL-10 but not tumor necrosis factor alpha (TNF-␣) in rats subjected to ZYA while reducing i.a. IL-10, but not IL-1␤ or TNF-␣, levels in mice. Clinically, mice subjected to CIA treated with the A. suum extract had less severe arthritis. Hypernociception, myeloperoxidase activity, and synovitis severity were significantly reduced. These data show that a helminth extract given p.o. protects from arthritis severity in two classical arthritis models. This A. suum effect is species independent and functions orally and parenterally. The results show clinical and structural benefits when A. suum extract is given either prophylactically or therapeutically.

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:

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SR provides analgesia in arthritis that is associated to inhibition of the release of inflammatory cytokines into inflamed joints. This effect is abrogated by administration of the opioid antagonist naloxone.

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