INHIBITING A SPINAL DYNORPHIN-A COMPONENT ENHANCES INTRATHECAL MORPHINE ANTINOCICEPTION IN MICE

Morphine given intracerebroventricularly releases spinal dynorphin A ( Dyn) in mice. The present study was undertaken to determine whether mo rphine given intrathecally (IT) released Dyn. We demonstrated that the antinociceptive action of morphine was enhanced by procedures that ar e known to attenuate Dyn action. First, coadministration of the opiate antagonists, naloxone (5 fg), norbinaltorphimine (5 fg) or beta-funal trexamine (0.25 ng) with IT morphine (0.15 mug, 5 n-tin) increased ant inociceptive percentage maximum possible effect (%MPE) from 30% to 65% . Second, dynorphin antiserum (5 mug, 1 h, IT), which neutralizes Dyn action, enhanced morphine (0.2 mug, 5 min, IT) action; MPE of 27% was increased to 60%. Third, production of desensitization to the antagoni stic action of Dyn, IT, by pretreatment with morphine [10 mg/kg, 3 h, subcutaneously (SC)], or 2 mug, 3 h, IT) or Dyn (1 ng, 1 h, IT) increa sed the 30% MPE of IT morphine to 60%. Naloxone [1 ng/kg, intraperiton eally (IP)] enhanced IT morphine at a peak time of 20 min. Nalmefene [ 1 to 100 ng/kg, per os (PO)] enhanced IT morphine action. In conclusio n, the present study showed that IT morphine putatively released spina l Dyn.