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A calcitonin gene-related peptide receptor antagonist prevents the development of tolerance to spinal morphine analgesia

DP Menard, D van Rossum, S Kar, S St Pierre, M Sutak, K Jhamandas and R Quirion
Journal of Neuroscience 1 April 1996, 16 (7) 2342-2351; DOI: https://doi.org/10.1523/JNEUROSCI.16-07-02342.1996
DP Menard
Douglas Hospital Research Center, McGill University, Verdun, Quebec, Canada.
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D van Rossum
Douglas Hospital Research Center, McGill University, Verdun, Quebec, Canada.
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S Kar
Douglas Hospital Research Center, McGill University, Verdun, Quebec, Canada.
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S St Pierre
Douglas Hospital Research Center, McGill University, Verdun, Quebec, Canada.
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M Sutak
Douglas Hospital Research Center, McGill University, Verdun, Quebec, Canada.
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K Jhamandas
Douglas Hospital Research Center, McGill University, Verdun, Quebec, Canada.
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R Quirion
Douglas Hospital Research Center, McGill University, Verdun, Quebec, Canada.
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Abstract

Tolerance to morphine analgesia is believed to result from a neuronal adaptation produced by continuous drug administration, although the precise mechanisms involved have yet to be established. Recently, we reported selective alterations in rat spinal calcitonin gene-related peptide (CGRP) markers in morphine-tolerant animals. In fact, increases in CGRP-like immunostaining and decrements in specific [125]hCGRP binding in the superficial laminae of the dorsal horn were correlated with the development of tolerance to the spinal antinociceptive action of morphine. Other spinally located peptides such as substance P, galanin, and neuropeptide Y were unaffected. Thus, the major goal of the present study was to investigate whether the development of tolerance to spinally infused morphine could be modulated by the blockade of dorsal horn CGRP receptors using the potent CGRP antagonist hCGRP(8–37). Indeed, cotreatments with hCGRP(8–37) prevented, in a dose- dependent manner, the development of tolerance to morphine-induced analgesia in both the rat tail-flick/tail-immersion and paw-pressure tests. Moreover, alterations in spinal CGRP markers seen in morphine- tolerant animals were not observed after a coadministration of morphine and hCGRP(8–37). These results demonstrate the existence of specific interaction between CGRP and the development of tolerance to the spinal antinociceptive effects of morphine. They also suggest that CGRP receptor antagonists could become useful adjuncts in the treatment of pain and tolerance to the antinociceptive effects of morphine.

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The Journal of Neuroscience: 16 (7)
Journal of Neuroscience
Vol. 16, Issue 7
1 Apr 1996
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A calcitonin gene-related peptide receptor antagonist prevents the development of tolerance to spinal morphine analgesia
DP Menard, D van Rossum, S Kar, S St Pierre, M Sutak, K Jhamandas, R Quirion
Journal of Neuroscience 1 April 1996, 16 (7) 2342-2351; DOI: 10.1523/JNEUROSCI.16-07-02342.1996

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A calcitonin gene-related peptide receptor antagonist prevents the development of tolerance to spinal morphine analgesia
DP Menard, D van Rossum, S Kar, S St Pierre, M Sutak, K Jhamandas, R Quirion
Journal of Neuroscience 1 April 1996, 16 (7) 2342-2351; DOI: 10.1523/JNEUROSCI.16-07-02342.1996
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