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Douleur et Analgésie

, Volume 10, Issue 4, pp 127–130 | Cite as

Les antagonistes de la cholécystokinine: futurs antalgiques?

Article

Résumé

La cholécystokinine (CCK) est présente dans le cerveau et la moelle épinière où elle agit comme neuromédiateur en activant deux types de récepteurs A et B, ce dernier étant prédominant dans le système nerveux central. Différentes études électrophysiologiques et comportementales plaident en faveur de l'existence d'une interaction entre les systèmes CCK-ergique et opioïde endogènes dans le contrôle de la nociception. Le système CCK-ergique a ainsi été qualifié de système anti-opioïdergique. Expérimentalement, l'administration d'un antagoniste CCK-B potentialise l'effet antinociceptif de la morphine. L'ensemble des données actuelles laisse entrevoir la possibilité d'utiliser des antagonistes CCK-B spécifiques et sélectifs comme analgésiques de complément à la morphine dans le traitement des douleurs postopératories ou chroniques sévères.

Summary

Cholecystokinin (CCK) is located in the brain and the spinal cord. CCK acts as a neuromediator and produces various biological effects that are mediated by two receptors: CCK-A and CCK-B, the predominant form found in the central nervous system. Electrophysiological and behavioural studies suggest the existence of regulatory mechanism between CCK and opioid systems in the control of pain. Thus, it has been proposed that CCK could act as an endogenous opiate and play a role in the development of morphine tolerance. In contrast, administration of a CCK-B receptor antagonist may enhance the antinociceptive effect of morphine. Experimental and clinical studies indicate the possibility for the therapeutic use of selective and specific CCK-B receptor antagonists as co-analgesics with morphine in postoperative period or in patient with intractable pain.

Key words

CCK CCK-B antagonists endogenous opioids nociception 

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Bibliographie

  1. 1.
    Baber N.S.: The role of CCK, caerulein, and CCK antagonist in nociception.Pain 39, 307–328, 1989.PubMedCrossRefGoogle Scholar
  2. 2.
    Durieux C.: Cholécystokinines et Gastrine.In:Neuropeptides et Neuromédiateurs. Coordinateur J. Epelbaum, Sandoz Ed., Paris, 1992.Google Scholar
  3. 3.
    Docray G.J.: Immunochemical evidence of CCK-like peptides in brain.Nature 264, 568–570, 1976.CrossRefGoogle Scholar
  4. 4.
    Kinze S.: Pharmacological characterization of CCKB receptors in human brain: no evidence for receptor heterogeneity.Neurescience Letter 217, 45–48, 1996.CrossRefGoogle Scholar
  5. 5.
    Lignon M.F.: CCK increases intracellular calcium concentration in the human Jurkat T Lymphocyte cell line.Eur. J. Pharmacol. 245, 241–246, 1993.PubMedCrossRefGoogle Scholar
  6. 6.
    Wang J.F.: Mobilization of calcium from intracellular stores as one of the mechanisms underlying the antiopiold effect of CCK-8.Peptides 13, 947–951, 1992.PubMedCrossRefGoogle Scholar
  7. 7.
    Yamamoto T.: The effects of intrathecally administered FK480, a cholecystokinin-A receptor antagonist, and YM022, a cholecystokinin-B receptor antagonist, on the formalin test in the rat.Anesth. Analg. 83, 107–113, 1996.PubMedCrossRefGoogle Scholar
  8. 8.
    Dourish G.T.: The selective CCKB receptor antagonist, L365.260 enhances morphine analgesia and prevents morphine tolerance in the rat.Eur. J. Pharmacol 234, 147–154, 1993.CrossRefGoogle Scholar
  9. 9.
    Noble F.: Modulation of opioid antinoception by CCK at the supraspinal level: evidence of regulatory mechanisms between CCK and enkephalin systems in the control of pain.Br. J. Pharmacol. 109, 1064–1070, 1993.PubMedGoogle Scholar
  10. 10.
    Paris P.L.: Evidence for the neuropeptide CCK as an antagonist of opiate analgesia.Science 219, 1449–1451, 1983.CrossRefGoogle Scholar
  11. 11.
    Stanfa L.: CCK as a factor in the enhanced potency of spinal morphine following carageenan inflammation.Br. J. Pharmacol. 108, 967–973, 1993.PubMedGoogle Scholar
  12. 12.
    Stanfa L.: CCK and morphine analgesia: variation on a theme.Trends Pharmacol. Sci. 88, 65–66, 1994.CrossRefGoogle Scholar
  13. 13.
    Xu T.: CCK-8 reverses the kappa-opioid-receptor-mediated depression of calcium current in rat dorsal root ganglion neurons.Brain Res. 730, 207–211, 1996.PubMedGoogle Scholar
  14. 14.
    Noble F.: Role of endogenous CCK in the facilitation of mu-mediated antinociception by delta opioid agonists.J. Pharmacol. Exp. Ther. 271, 1127–1134, 1994.PubMedGoogle Scholar
  15. 15.
    Bnoliel J.J.: Mu and delta receptors mediate opposite modulations by morphine of the spinal release of CCK-like material.Brain Res. 653, 81–91, 1994.CrossRefGoogle Scholar
  16. 16.
    Migaud M.: Effects of CCK-8 and BC264, a potent and selective CCKB agonist on asparate and glutamate release from rat hippocampal slices.Neuropharmacol. 33, 737–743, 1994.CrossRefGoogle Scholar
  17. 17.
    Pu S.F.: Cholecystokinine octapeptide antagonizes morphine analgesia in nucleus accumbens of the rat via the CCK-B receptor.Brain Res. 657, 159–164, 1994.PubMedCrossRefGoogle Scholar
  18. 18.
    Zhou Y.: Accelerated expression of CCK gene in the brain of rats rendered tolerant to morphine.Neuroreport 3, 1121–1123, 1992.PubMedCrossRefGoogle Scholar
  19. 19.
    Xu X.J.: The CCKB antagonist CI988 enhances the reflex-depressive effect of morphine in axotomized rats.Neuroreport 5, 718–720, 1994.PubMedGoogle Scholar
  20. 20.
    Pu S.F.: CCK gene expression in rat amygdaloid neurons: normal distribution and effect of morphine tolerance.Brain Res. Mol. 21, 183–189, 1994.CrossRefGoogle Scholar
  21. 21.
    Benedetti F.: The opposite, effects of the opiate antagonist naloxone and the CCK antagonist proglumide on placebo analgesia.Pain 64, 535–543, 1996.PubMedCrossRefGoogle Scholar
  22. 22.
    Lavigne G. Proglumide potentiates morphine analgesia for acute postchirurgical pain.Clin. Pharmacol. Ther. 45, 666–673, 1989.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • C. Mann
    • 1
  1. 1.Centre Anti-Douleur, Hôpital Saint-EloiCHU MontpellierMontpellier Cedex 5

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