Dynorphin Promotes Abnormal Pain and Spinal Opioid Antinociceptive Tolerance

• DOI: 10.1523/jneurosci.20-18-07074.2000
• Publication Date: 2018-04-05T22:26:18Z
• Authors: Todd W. Vanderah; Luis R. Gardell; Shannon E. Burgess; Mohab Ibrahim; Ahmet Dogrul; Cheng-Min Zhong; En-Tan Zhang; T. Philip Malan; Michael H. Ossipov; Josephine Lai; Frank Porreca
• Keywords: Dynorphin; DAMGO; Dynorphin A; Spinal nerve; Allodynia

The nonopioid actions of spinal dynorphin may promote aspects abnormal pain after nerve injury. Mechanistic similarities have been suggested between opioid tolerance and neuropathic pain. Here, the hypothesis that might mediate effects sustained opioids was explored. Possible antinociceptive were evaluated intrathecal administration [d-Ala²,<i>N</i>-Me-Phe⁴, Gly-ol⁵]enkephalin (DAMGO), an μ agonist. Rats infused with DAMGO, but not saline, demonstrated tactile allodynia thermal hyperalgesia hindpaws (during DAMGO infusion) a decrease in potency efficacy (tolerance), signs also characteristic Spinal elicited increase lumbar content receptor immunoreactivity dorsal horn, seen postnerve-injury state. Intrathecal A(1–17) antiserum blocked reversed to above baseline levels (i.e., antinociception). antiserum, control serum, reestablished morphine. Neither nor serum altered non-noxious or noxious thresholds affected morphine response saline-infused rats. These data suggest promotes acts reduce tolerance). identify possible mechanism for previously unexplained clinical observations offer novel approach development strategies could improve long-term use