Effects of paracetamol and aspirin on neural activity of joint mechanonociceptors in adjuvant arthritis.
1. 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. 2. 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. 3. The prostanoid IP receptor agonist, cicaprost (0.1-0.5 micrograms), 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. 4. 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. 5. 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.
McQueen
D S
DS
Department of Pharmacology, University of Edinburgh Medical School.
Iggo
A
A
Birrell
G J
GJ
Grubb
B D
BD
D000082:Acetaminophen / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000503:physiopathology*; D001241:Aspirin / Q000031:analogs & derivatives / Q000494:pharmacology*; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects*; D009431:Neural Conduction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012459:Salicylates / Q000097:blood / Q000494:pharmacology; D012684:Sensory Thresholds / Q000187:drug effects; D013643:Tarsus, Animal / Q000294:innervation / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012459:Salicylates; D000082:Acetaminophen; D011464:Epoprostenol; D008239:Lysine; C043867:cicaprost; D001241:Aspirin; C010395:acetylsalicylic acid lysinate