<strong><strong>Changes of CGRP8-37-induced Antinociception and CGRP-immunoreactivity at Spinal Levels in Morphine Tolerant Rats </strong></strong>

Abstract

Abstract:Objective: It is known that intrathecal administration of calcitonin gene-related peptide 8-37 (CGRP8-37), an antagonist to CGRP1 receptor, induced antinociception. The present study was performed to investigate the changes in nociceptive modulation of CGRP8-37 and CGRP-immunoreactivity at spinal levels after morphine tolerance.Methods: The hindpaw withdrawal latencies (HWLs) to both thermal and mechanical stimulation were assessed by hot plate and Randall Selitto Test. The CGRP-like immunoreactivity at spinal levels was tested by immunohistochemistry.Results:The hindpaw withdrawal latencies (HWLs) to both thermal and mechanical stimulation increased significantly after intrathecal injection of 10 nmol of CGRP8-37. There were also significant increases in HWLs to both thermal and mechanical stimulation after intrathecal administration of CGRP8-37 in morphine tolerant rats and rats recovered from morphine tolerance. It is interesting that the CGRP8-37-induced antinociceptive effects were lower in morphine tolerant rats than those in morphine naive rats and rats recovered from morphine tolerance. Furthermore, there were increases in CGRP-like immunoreactivity in dorsal horn of the spinal cord and the dorsal root ganglia (DRG) of L3 – L5 in morphine tolerant rats.Conclusion: The results of the present study demonstrated the down-regulations in CGRP8-37-induced antinociception after morphine tolerance, which is possibly resulted from the changes in both the opioid and the CGRP systems. The latter was implicated partly in the present study, in that there were plastic changes in CGRP-like immunoreactivity in dorsal horn and DRG after morphine tolerance. All results above suggested that CGRP might play an important role in morphine tolerance at the spinal levels.

Key words:antinociception,calcitonin gene-related peptide (CGRP),CGRP8-37,morphine tolerance,spinal cord,dorsal root ganglia (DRG)

YANG Ying, YU Long-Chuan.Changes of CGRP8-37-induced Antinociception and CGRP-immunoreactivity at Spinal Levels in Morphine Tolerant Rats[J]. Acta Neuropharmacologica, 2013, 3(2): 1-12.

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Changes of CGRP8-37-induced Antinociception and CGRP-immunoreactivity at Spinal Levels in Morphine Tolerant Rats

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