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Synaptic Plasticity in Pain pp 353–366Cite as

Spinal Dynorphin and Neuropathic Pain

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Abstract

The endogenous neuropeptides dynorphins are proteolytic products of prodynorphin which are characterized by their high affinity for opioid receptors. Dynorphin A is widely distributed in the CNS and in the spinal cord is found predominantly in neurons of laminae I/II and V. Intrathecal dynorphin A displays predominantly non-opioid activities which can be reversed by NMDA antagonists as well as by bradykinin B2 receptor antagonists. The levels of spinal dynorphin expression can be easily perturbed; elevated levels of dynorphin A in the spinal cord are essential for the expression of chronic pain. Descending modulatory pain pathways from the rostral ventromedial medulla contribute to dynorphin up-regulation and the maintenance of neuropathic pain. Recovery from neuropathic pain may depend not only on recovery from the peripheral injury but also on reversing the injury-induced adaptive changes to the central nervous system such as dynorphin up-regulation.

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Abbreviations

cAMP:

cyclic adenosine monophosphate

CGRP:

calcitonin gene-related peptide

DALBK:

des-Arg9Leu-bradykinin

DLF:

dorsolateral funiculus

DREAM:

downstream regulatory element antagonistic modulator

DRG:

dorsal root ganglion

i.c.v.:

intracerebroventricularly

i.t.:

intrathecally

NMDA:

N-methyl-d-aspartate

NPY:

neuropeptide Y

RVM:

rostral ventral medulla

SNL:

spinal nerve ligation

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Acknowledgments

The work presented in this review has been supported by grants from the National Institute on Drug Abuse (F.P.) and the National Institute of Dental and Craniofacial Research (J.L.).

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  1. Department of Pharmacology, University of Arizona Health Sciences Center, Tucson, AZ 85724, USA

    Josephine Lai, Ruizhong Wang & Frank Porreca

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  1. Josephine Lai
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Correspondence to Frank Porreca .

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    Lai, J., Wang, R., Porreca, F. (2009). Spinal Dynorphin and Neuropathic Pain. In: Malcangio, M. (eds) Synaptic Plasticity in Pain. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0226-9_16

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