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.