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Involvement of brain serotonergic system in the antinociceptive action of acetylsalicylic acid in the rat

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Abstract

The pain-threshold in the hot-plate test and serotonin (5-HT) receptor binding capacity in the cortex and pontine areas of rat brain were studied after intraperitoneal (ip) administration of acetyl salicylate of lysine equivalent to 400 mg/kg of acetylsalicylic acid (ASA). The antinociceptive activity of ASA was prevented by ip pre-treatment with Parachlorophenylalanine (PCPA) at the rate of 100 mg/kg/day for 4 days. PCPA pre-treatment increased the number of 5-HT receptors and abolished the ASA-induced reduction in 5-HT receptor binding capacity in the cortex but did not affect serum salicylate levels. These results provide support for the hypothesis that the antinociceptive action of ASA, at least in the hot-plate test, involves the central serotonergic system.

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References

  1. Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature New Biol 1971;231:232–5.

    Google Scholar 

  2. Hunskaar S. Similar effects of acetylsalicylic acid and morphine on immediate responses to acute noxious stimulation. Pharmacol and Toxicol 1987;60:167–70.

    Google Scholar 

  3. Brune K, Beck WS, Geisslinger G, Menzel-Soglowek S, Peskar BM, Peskar BA. Aspirin-like drugs may block pain independently of prostaglandin synthesis inhibition. Experientia 1991;47:257–61.

    Google Scholar 

  4. Abramson SV, Weissman G. The mechanism of action of non-steroidal anti-inflammatory drugs. Arthr Rheumat 1989;32:1–9.

    Google Scholar 

  5. McCormack K, Brune K. Dissociation between the antinociceptive and anti-inflammatory effects of the nonsteroidal anti-inflammatory drugs. Drugs 1991;41:533–47.

    Google Scholar 

  6. Shyu KW, Lin MT. Hypothalamic monoaminergic mechanisms of aspirin-induced analgesia in monkeys. J Neural Trans 1985;62:285–8.

    Google Scholar 

  7. Gelgor L, Cartmell S, Mitchell D. Intracerebroventricular micro-injections of non-steroidal anti-inflammatory drugs abolish reperfusion hyperalgesia in the rat's tail. Pain 1992;50:323–9.

    Google Scholar 

  8. Nichols D, Thorn BE, Berntson GC. Opiate and serotonergic mechanism of stimulation-produced analgesia within the periaqueductal gray. Brain Res Bull 1989;22:717–20.

    Google Scholar 

  9. Pascual J. Serotonin, serotonin receptors, serotonin receptor subtype agonists and pain. Pain 1990;40:115–6.

    Google Scholar 

  10. Kobal G, Hummel C, Neurnberg B, Brune K. Effects of pentazocine and acetylsalicylic acid on pain-rating, pain-related evoked potentials and vigilance in relationship to pharmacokinetic parameters. Agents Actions 1990;29:342–59.

    Google Scholar 

  11. Wang J-P, Teng CM. Effects of anti-inflamatory drugs on rat hind-paw swelling caused by phospholipase A2 from Naja naja atra venom. Naunyn-Schmiedeberg's Arch Pharmacol 1991;344:377–81.

    Google Scholar 

  12. Buzzi MG, Sakas DE, Moskowitz M A. Indomethacin and acetylsalicylic acid block neurogenic plasma protein extravasation in rat dura mater. Europ J Pharmacol 1989;165:251–8.

    Google Scholar 

  13. Woolf CJ. Central and peripheral components of hyperalgesia that follows peripheral tissue injury, In: Rowe M, Willis WD eds: Development, organization and processing in somatosensory pathways, New York: Alan R Liss Inc, New York, 1985; pp 317–23.

    Google Scholar 

  14. Wood PI. Animal models in analgesic testing, in: Analgesics: neurochemical, behavioural and clinical perspectives. (Kuhar M and Pasternak G eds) New York: Raven Press, 1984; pp 175–193.

    Google Scholar 

  15. Groppetti A, Braga PC, Biella G, Parenti M, Rusconi L, Mantegazza P. Effect of aspirin on serotonin and metenkephalin in brain: correlation with the antinociceptive activity of the drug. Neuropharmacol 1988;27:499–505.

    Google Scholar 

  16. Pini LA, Vitale G, Sandrini M. Chronic treatment with phenazone modifies pontine noradrenergic receptors in rats. In: F Clifford Rose, ed, New Advances in headache research 2. London: Smith-Gordon, 1991; pp 293–297.

    Google Scholar 

  17. Pini LA, Vitale G, Sandrini M. Brain serotonin binding capacity, analgesia and drug serum levels after acute treatment with phenazone in rats. Pharmacol Res 1992;25 (2S):258–9.

    Google Scholar 

  18. Zimmermann M. Ethical guidelines for investigation of experimental pain in conscious animals. Pain 1983;16:109–10.

    Google Scholar 

  19. Hunskaar S, Berge O-G, Hole K. A modified hot-plate test sensitive to mild analgesics. Behav Brain Res 1986;21:101–8.

    Google Scholar 

  20. Bjørklund A, Dunnett SB, Stenevi U, Lewis ME, Iversen SD. Reinnervation of the denerved striatum by substantia nigra transplants: function consequences as revealed by pharmacological and sensomotor testing. Brain Res 1980;199:307–33.

    Google Scholar 

  21. Bures J, Buresova O, Huston J. Innate and motivate behaviour. In: Technique and basic experiments for the study of brain and behaviour, Amsterdam: Elsevier Sc Publishers B.V. 1983: pp 77–84.

    Google Scholar 

  22. Harris LS, Pierson AK. Some narcotic antagonists in the benzomorphin series. J Pharmacol Expl Ther 1964;143:141–5.

    Google Scholar 

  23. Bennet JP, Snyder SH. Serotonin and lysergic acid diethylamide binding in rat brain membranes: relationship to postsynaptic serotonin receptors. Mol Pharmacol 1976;12:373–89.

    Google Scholar 

  24. Rosenthal H. A graphic method for the determination and presentation of binding parameters in a complex system. Anal Biochem 1967;20:520–32.

    Google Scholar 

  25. Dubas TC, Parker JM. A central component in the analgesic action of sodium salicylate. Arch Int Pharmacodyn 1971;194:117–22.

    Google Scholar 

  26. Sandrini M, Vitale G, Sternieri E, Bertolini A, Pini LA. Effect of chronic treatment of phenazone on the hot-plate test and [3H]-serotonin binding sites in pons and cortex membranes in the rat. Pharmacol 1993;47:84–90.

    Google Scholar 

  27. Hunskaar S, Berge O-G, Hole K. Dissociation between antinociceptive and anti-inflammatory effects of acetylsalicylic acid and indomethacin in the formalin test. Pain 1986;25:125–32.

    Google Scholar 

  28. Pong SF, Demuth SM, Kinney CM, Deegan P. Prediction of human analgesic dosages of nonsteroidal anti-inflammatory drugs (NSAIDs) from analgesic ED50 values in mice. Arch Int Pharmacodyn 1985;273:212–20.

    Google Scholar 

  29. Taber RI, Latranyi MB. Antagonism of the analgesic effect of opioid and non-opioid agents by p-chlorophenylalanine (PCPA). Europ J Pharmacol 1981;75:215–22.

    Google Scholar 

  30. Pini LA, Vitale G, Sandrini M. The role of serotonin brain receptors in the analgesic effect of phenazone. Drugs Exptl Clin Res 1993;19:13–17.

    Google Scholar 

  31. Bensemana D, Gascon AL. Relationship between analgesia and turnover of brain biogenic amines. Can J Physiol Pharmacol 1978;56:721–30.

    Google Scholar 

  32. Chapman V, Dickenson AH. The spinal and peripheral roles of bradykinin and prostaglandins in nociceptive processing in the rat. Europ J Pharmacol 1992;219:427–33.

    Google Scholar 

  33. Malmberg AB, Yaksh TL. Antinociceptive actions of spinal nonsteroidal anti-inflammatory agents on the formalin test in the rat. J Pharmacol Exp Ther 1992;263:136–46.

    Google Scholar 

  34. Hunskaar S, Farmer OB, Hole K. Acetylsalicylic acid, paracetamol and morphine inhibit behaviour responses to intrathecally administered substance P or Capsaicin. Life Sci 1985;37:1835–41.

    Google Scholar 

  35. Brune K, Menzel-Soglowek S, Zeilhofer HU. Differential analgesic effect of aspirin-like drugs. Drugs 1992;44 (5S):52–9.

    Google Scholar 

  36. Hoffmann P, Skarphedinsson JD, Delle M, Thoren P. Electrical stimulation of the gastrocnemius muscle in the spontaneously hypertensive rat increases the pain threshold: role of different serotonergic receptors. Acta Physiol Scand 1990;138:125–31.

    Google Scholar 

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Authors and Affiliations

  1. Clinical Pharmacology Unit, University of Modena, via del Pozzo, 71, I-41100, Modena, Italy

    L. A. Pini & G. Vitale

  2. Biomedical Sciences Dept., University of Modena, via del Pozzo, 71, I-41100, Modena, Italy

    M. Sandrini

Authors
  1. L. A. Pini
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  2. M. Sandrini
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  3. G. Vitale
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Pini, L.A., Sandrini, M. & Vitale, G. Involvement of brain serotonergic system in the antinociceptive action of acetylsalicylic acid in the rat. Inflamm Res 44, 30–35 (1995). https://doi.org/10.1007/BF01630485

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  • DOI: https://doi.org/10.1007/BF01630485

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