Spinal Dynorphin and Neuropathic Pain



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.


NMDA Receptor Neuropathic Pain Opioid Receptor Spinal Nerve Ligation Kappa Opioid Receptor 



cyclic adenosine monophosphate


calcitonin gene-related peptide




dorsolateral funiculus


downstream regulatory element antagonistic modulator


dorsal root ganglion








neuropeptide Y


rostral ventral medulla


spinal nerve ligation



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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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of PharmacologyUniversity of Arizona Health Sciences CenterTucsonUSA

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