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CGRP in Spinal Cord Pain Mechanisms

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Synaptic Plasticity in Pain

Abstract

Calcitonin gene-related peptide (CGRP) has emerged as an important molecule at different levels of the pain neuraxis. Anatomical, neurochemical, electrophysiological and behavioral data strongly suggest that CGRP in the spinal cord enhances neurotransmission, neuronal excitability, and nocifensive behaviors in preclinical pain models. Spinal CGRP also modulates the transmission of nociceptive information to supraspinal sites, thus contributing to high integrated pain behaviors. The precise mechanism of action of CGRP is still not fully understood, in part because of the complexity of the CGRP receptor(s). There is strong evidence for postsynaptic actions in the spinal cord, but CGRP receptors appear to be localized on both pre- and post-synaptic elements and can modulate the release and action of other transmitters as well. The availability of CGRP antagonists that have been tested successfully in Phase II clinical trials for migraine headache offers an important opportunity for new and improved therapeutic strategies in certain pain states.

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Abbreviations

CLR:

calcitonin-like receptors

DAMGO:

[D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin

GPCRs:

G-protein coupled receptors

NO:

nitric oxyde

PKA:

protein kinase A

PKC:

protein kinase C

RAMP1:

receptor activity-modifying protein 1

RCP:

receptor component protein

VGLUT2:

vesicular glutamate transporter -2

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Acknowledgments

The author’s work is supported by NIH grants NS38261 and NS11255.

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  1. Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, TX 77555-1069, USA

    Volker Neugebauer

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    Neugebauer, V. (2009). CGRP in Spinal Cord Pain Mechanisms. In: Malcangio, M. (eds) Synaptic Plasticity in Pain. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0226-9_8

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