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.
KeywordsNMDA Receptor Neuropathic Pain Opioid Receptor Spinal Nerve Ligation Kappa Opioid Receptor
cyclic adenosine monophosphate
calcitonin gene-related peptide
downstream regulatory element antagonistic modulator
dorsal root ganglion
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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