title: The Emerging Role of Spinal Dynorphin in Chronic Pain: A Therapeutic Perspective.
abstract: Notable findings point to the significance of the dynorphin peptide neurotransmitter in chronic pain. Spinal dynorphin neuropeptide levels are elevated during development of chronic pain and sustained during persistent chronic pain. Importantly, knockout of the dynorphin gene prevents development of chronic pain in mice, but acute nociception is unaffected. Intrathecal (IT) administration of opioid and nonopioid dynorphin peptides initiates allodynia through a nonopioid receptor mechanism; furthermore, antidynorphin antibodies administered by the IT route attenuate chronic pain. Thus, this review presents the compelling evidence in the field that supports the role of dynorphin in facilitating the development of a persistent pain state. These observations illustrate the importance of elucidating the control mechanisms responsible for the upregulation of spinal dynorphin in chronic pain. Also, spinal dynorphin regulation of downstream signaling molecules may be implicated in hyperpathic states. Therapeutic strategies to block the upregulation of spinal dynorphin may provide a nonaddictive approach to improve the devastating condition of chronic pain that occurs in numerous human diseases.
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093; email: vhook@ucsd.edu.
authors.forename: Sonia
authors.initials: S
authors.lastname: Podvin
authors.affiliation: Department of Anesthesiology.
authors.forename: Tony
authors.initials: T
authors.lastname: Yaksh
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093; email: vhook@ucsd.edu.|Department of Neurosciences, and.|Department of Pharmacology, University of California, San Diego School of Medicine, La Jolla, California 92093.
authors.forename: Vivian
authors.initials: V
authors.lastname: Hook
mesh_terms: D000818:Animals; D059350:Chronic Pain / Q000188:drug therapy* / Q000378:metabolism*; D004399:Dynorphins / Q000378:metabolism*; D006801:Humans; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004399:Dynorphins
keywords: chronic pain; dynorphin; glia; neuron; secretory vesicles; spinal cord; spinal ganglia