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Science 8 May 1992:
Vol. 256. no. 5058, pp. 830 - 833
DOI: 10.1126/science.1589765
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Articles

Science, Vol 256, Issue 5058, 830-833
Copyright © 1992 by American Association for the Advancement of Science

articles

Cholecystokinin antianalgesia: safety cues abolish morphine analgesia

EP Wiertelak, SF Maier, and LR Watkins

Department of Psychology, University of Colorado, Boulder 80309.

Environmental stimuli that signal the occurrence of aversive or dangerous events activate endogenous opiate analgesia systems. Signals for safety (the nonoccurrence of aversive events) produce the opposite and inhibit environmentally produced analgesia. Stimuli that signal safety are now shown to abolish the analgesic effect of morphine, even when morphine is applied directly to spinal cord. Further, this antiopiate effect occurs because the environmental stimulus leads to release of the neuropeptide cholecystokinin in the spinal cord. This process may contribute to the regulation of pain and the development of opiate tolerance.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Neural Basis for the Hyperalgesic Action of Cholecystokinin in the Rostral Ventromedial Medulla.
M. M. Heinricher and M. J. Neubert (2004)
J Neurophysiol 92, 1982-1989
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Inhibition of Neuropathic Pain by Selective Ablation of Brainstem Medullary Cells Expressing the {micro}-Opioid Receptor.
F. Porreca, S. E. Burgess, L. R. Gardell, T. W. Vanderah, T. P. Malan Jr, M. H. Ossipov, D. A. Lappi, and J. Lai (2001)
J. Neurosci. 21, 5281-5288
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Inverse Agonist Action of Leu-Enkephalin at delta 2-Opioid Receptors Mediates Spinal Antianalgesia.
J. J. Rady, B. B. Holmes, L. F. Tseng, and J. M. Fujimoto (2001)
J. Pharmacol. Exp. Ther. 297, 582-589
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Circuitry Underlying Antiopioid Actions of Cholecystokinin Within the Rostral Ventromedial Medulla.
M. M. Heinricher, S. McGaraughty, and V. Tortorici (2001)
J Neurophysiol 85, 280-286
   Abstract »    Full Text »    PDF »
Mutations within the Cholecystokinin-B/Gastrin Receptor Ligand `Pocket' Interconvert the Functions of Nonpeptide Agonists and Antagonists.
M. Bläker, Y. Ren, M. C. Gordon, J. E. Hsu, M. Beinborn, and A. S. Kopin (1998)
Mol. Pharmacol. 54, 857-863
   Abstract »    Full Text »
Interspecies Polymorphisms Confer Constitutive Activity to the Mastomys Cholecystokinin-B/Gastrin Receptor.
K. Schaffer, E. W. McBride, M. Beinborn, and A. S. Kopin (1998)
J. Biol. Chem. 273, 28779-28784
   Abstract »    Full Text »    PDF »
Pentobarbital Antagonism of Morphine Analgesia Mediated by Spinal Cholecystokinin.
J. J. Rady, W. Lin, and J. M. Fujimoto (1998)
J. Pharmacol. Exp. Ther. 284, 878-885
   Abstract »    Full Text »
Inter- and intraspecies polymorphisms in the cholecystokinin-B/gastrin receptor alter drug efficacy.
A. S. Kopin, E. W. McBride, M. C. Gordon, S. M. Quinn, and M. Beinborn (1997)
PNAS 94, 11043-11048
   Abstract »    Full Text »    PDF »


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