Effects of paracetamol and aspirin on neural activity of joint mechanonociceptors in adjuvant arthritis

The effects of paracetamol and lysine acetylsalicylate (L‐AS) on high‐threshold mechanonociceptors have been investigated by recording neural activity from the inflamed ankle joint in anaesthetized rats with mild adjuvant‐induced monoarthritis. Paracetamol (50 mg kg⁻¹, i.v.) and L‐AS (100 mg kg⁻¹, i.v., equivalent to 50 mg kg⁻¹ aspirin) both caused a maximal reduction of about 40% in mechanically‐evoked discharge and of 30% in ongoing (spontaneous) activity by about 15 min after the injection: a second dose of either drug did not have any significant additional effect on discharge. The prostanoid IP receptor agonist, cicaprost (0.1–0.5 μg), increased both mechanically‐evoked and ongoing discharge to pre‐paracetamol levels when injected close‐arterially 30–50 min after paracetamol, whereas prostaglandin E₂ (PGE₂) was relatively ineffective at restoring activity. The results suggest that prostacyclin (PGI₂) contributes to the sensitization of high‐threshold joint mechanonociceptors in adjuvant‐induced monoarthritis, and that paracetamol and L‐AS both act to reduce discharge by inhibiting the synthesis of prostacyclin in the joint capsule. Paracetamol has a direct peripheral action affecting joint capsule mechanonociceptors in rat adjuvant‐induced arthritis which is very similar to that of the soluble aspirin preparation, L‐AS. These findings, together with the existing literature concerning the anti‐arthritic effects of paracetamol, are relevant to the treatment of chronic inflammatory disorders such as rheumatoid arthritis. 1991 British Pharmacological Society