Pronociceptive Actions of Dynorphin Maintain Chronic Neuropathic Pain

• DOI: 10.1523/jneurosci.21-05-01779.2001
• Publication Date: 2018-04-06T18:26:24Z
• Authors: Zaijie Wang; Luis R. Gardell; Michael H. Ossipov; Todd W. Vanderah; Miles B. Brennan; Ute Hochgeschwender; Victor J. Hruby; T. Phil Malan; Josephine Lai; Frank Porreca
• Keywords: Dynorphin; Dynorphin A

Whereas tissue injury increases spinal dynorphin expression, the functional relevance of this upregulation to persistent pain is unknown. Here, mice lacking prodynorphin gene were studied for sensitivity non-noxious and noxious stimuli, before after induction experimental neuropathic pain. Prodynorphin knock-out (KO) had normal responses acute stimuli a mild increased some stimuli. After nerve ligation (SNL), both wild-type (WT) KO demonstrated decreased thresholds innocuous mechanical thermal indicating that not required initiation However, whereas was sustained in WT mice, showed return baselines by post-SNL day 10. In SNL upregulated lumbar content on 10, but 2, injury. Intrathecal antiserum reversed at 10 (when upregulated) 2; intrathecal MK-801 SNL-pain times. Opioid (μ, δ, κ) receptor density G-protein activation different between unchanged The observations suggest (1) an early, dynorphin-independent phase later dynorphin-dependent stage, (2) pronociceptive maintenance pain, (3) processes state are distinct. Identification mechanisms maintain appears important strategies treat