Dynorphin-(1-13): antinociceptive action and its effects on morphine analgesia and acute tolerance

Antinociceptive actions and effects of intracerebroventricular (i.c.v.) dynorphin-(1-13) (DYN) on morphine (MOR) analgesia and acute tolerance were studied in male Sprague-Dawley rats. Antinociceptive effect against hind paw pressure was produced by 30 micrograms of DYN, but not by 0.5-10 micrograms. Acetic acid writhing was inhibited dose-dependently by DYN at the doses of 2-30 micrograms, and the order of potency of the anti-writhing effect was beta-endorphin > MOR > DYN >> Met-enkephalin. The anti-writhing effect of DYN that was partially antagonized by naloxone at 10 mg/kg, s.c. in MOR tolerant rats was the same as that in MOR naive rats. The anti-writhing effect of i.c.v.-MOR was increased synergistically by DYN. Continuous s.c. (6 mg/kg/hr) and i.c.v. (7.5 micrograms/rat/hr) infusion of MOR produced antinociception against hind paw pressure, which reached maximum (MAX) and attenuated thereafter during MOR infusion for 6 hr. The attenuation of antinociception was also produced during MOR infusion combined with multiple i.c.v.-injection of DYN. The MAX and area under the antinociceptive curve during MOR infusion was not affected by multiple injection of DYN, i.e., no effect of i.c.v.-DYN on the development of acute MOR tolerance induced by s.c.- and i.c.v.-infusion was observed. In conclusion, the anti-writhing effect of i.c.v.-DYN might not be mediated via mu-receptors, although DYN increased the anti-writhing effect of i.c.v.-MOR synergistically and the development of acute tolerance to MOR (i.c.v., s.c.) was not affected by i.c.v.-DYN.