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. 1991 Sep;104(1):178–182. doi: 10.1111/j.1476-5381.1991.tb12404.x

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

D S McQueen 1, A Iggo 1, G J Birrell 1, B D Grubb 1
PMCID: PMC1908301  PMID: 1786510

Abstract

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.

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Selected References

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  1. Adriaenssens P. I., Prescott L. F. High performance liquid chromatographic estimation of paracetamol metabolites in plasma. Br J Clin Pharmacol. 1978 Jul;6(1):87–88. doi: 10.1111/j.1365-2125.1978.tb01687.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Birrell G. J., McQueen D. S., Iggo A., Coleman R. A., Grubb B. D. PGI2-induced activation and sensitization of articular mechanonociceptors. Neurosci Lett. 1991 Mar 11;124(1):5–8. doi: 10.1016/0304-3940(91)90809-8. [DOI] [PubMed] [Google Scholar]
  3. Ferreira S. H., Lorenzetti B. B., Corrêa F. M. Central and peripheral antialgesic action of aspirin-like drugs. Eur J Pharmacol. 1978 Dec 15;53(1):39–48. doi: 10.1016/0014-2999(78)90265-0. [DOI] [PubMed] [Google Scholar]
  4. Ferreira S. H. Prostaglandins, aspirin-like drugs and analgesia. Nat New Biol. 1972 Dec 13;240(102):200–203. doi: 10.1038/newbio240200a0. [DOI] [PubMed] [Google Scholar]
  5. Grubb B. D., Birrell G. J., McQueen D. S., Iggo A. The role of PGE2 in the sensitization of mechanoreceptors in normal and inflamed ankle joints of the rat. Exp Brain Res. 1991;84(2):383–392. doi: 10.1007/BF00231460. [DOI] [PubMed] [Google Scholar]
  6. Grubb B. D., McQueen D. S., Iggo A., Birrell G. J., Dutia M. B. A study of 5-HT-receptors associated with afferent nerves located in normal and inflamed rat ankle joints. Agents Actions. 1988 Dec;25(3-4):216–218. doi: 10.1007/BF01965015. [DOI] [PubMed] [Google Scholar]
  7. Guilbaud G., Iggo A., Tegnér R. Sensory receptors in ankle joint capsules of normal and arthritic rats. Exp Brain Res. 1985;58(1):29–40. doi: 10.1007/BF00238950. [DOI] [PubMed] [Google Scholar]
  8. Guilbaud G., Iggo A. The effect of lysine acetylsalicylate on joint capsule mechanoreceptors in rats with polyarthritis. Exp Brain Res. 1985;61(1):164–168. doi: 10.1007/BF00235631. [DOI] [PubMed] [Google Scholar]
  9. Higgs G. A., Harvey E. A., Ferreira S. H., Vane J. R. The effects of antiinflammatory drugs on the production of prostaglandins in vivo. Adv Prostaglandin Thromboxane Res. 1976;1:105–110. [PubMed] [Google Scholar]
  10. Martin H. A., Basbaum A. I., Kwiat G. C., Goetzl E. J., Levine J. D. Leukotriene and prostaglandin sensitization of cutaneous high-threshold C- and A-delta mechanonociceptors in the hairy skin of rat hindlimbs. Neuroscience. 1987 Aug;22(2):651–659. doi: 10.1016/0306-4522(87)90360-5. [DOI] [PubMed] [Google Scholar]
  11. McQueen D. S., Ritchie I. M., Birrell G. J. Arterial chemoreceptor involvement in salicylate-induced hyperventilation in rats. Br J Pharmacol. 1989 Oct;98(2):413–424. doi: 10.1111/j.1476-5381.1989.tb12612.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. McQueen E. G. Anti-inflammatory drug mechanisms. Drugs. 1973;6(2):104–117. doi: 10.2165/00003495-197306020-00004. [DOI] [PubMed] [Google Scholar]
  13. Moncada S., Ferreira S. H., Vane J. R. Inhibition of prostaglandin biosynthesis as the mechanism of analgesia of aspirin-like drugs in the dog knee joint. Eur J Pharmacol. 1975 Apr;31(2):250–260. doi: 10.1016/0014-2999(75)90047-3. [DOI] [PubMed] [Google Scholar]
  14. Schaible H. G., Schmidt R. F. Activation of groups III and IV sensory units in medial articular nerve by local mechanical stimulation of knee joint. J Neurophysiol. 1983 Jan;49(1):35–44. doi: 10.1152/jn.1983.49.1.35. [DOI] [PubMed] [Google Scholar]
  15. Skjelbred P., Album B., Lokken P. Acetylsalicylic acid vs paracetamol: effects on post-operative course. Eur J Clin Pharmacol. 1977 Dec 2;12(4):257–264. doi: 10.1007/BF00607424. [DOI] [PubMed] [Google Scholar]
  16. Skuballa W., Schillinger E., Stürzebecher C. S., Vorbrüggen H. Synthesis of a new chemically and metabolically stable prostacyclin analogue with high and long-lasting oral activity. J Med Chem. 1986 Mar;29(3):313–315. doi: 10.1021/jm00153a001. [DOI] [PubMed] [Google Scholar]
  17. Vinegar R., Truax J. F., Selph J. L. Quantitative comparison of the analgesic and anti-inflammatory activities of aspirin, phenacetin and acetaminophen in rodents. Eur J Pharmacol. 1976 May;37(1):23–30. doi: 10.1016/0014-2999(76)90004-2. [DOI] [PubMed] [Google Scholar]
  18. Wong S., Gardocki J. F. Anti-inflammatory and antiarthritic evaluation of acetaminophen and its potentiation of tolmetin. J Pharmacol Exp Ther. 1983 Aug;226(2):625–632. [PubMed] [Google Scholar]

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