Inhibition of spinal opioid antinociception by intrathecal beta-endorphin1-27 in the rat.

1. The effects of intrathecal (i.t.) administration of beta-endorphin and two shorter fragments, human and ovine beta-endorphin1-27, were examined for antinociceptive activity in the tail-flick and paw-pressure tests in the rat. Additionally, the ability of ovine beta-endorphin1-27 to influence the action of i.t. beta-endorphin, morphine and [D-Pen2-D-Pen5]enkephalin (DPDPE) was also examined in these tests. 2. After i.t. injection, beta-endorphin produced potent dose-related antinociception in the tail-flick and paw-pressure tests. Shorter endorphins produced much weaker effects. The order of antinociceptive efficacy was beta-endorphin > human beta-endorphin1-27 > ovine beta-endorphin1-27. 3. Administration of ovine beta-endorphin1-27 (0.72, 1.44 nmol, i.t.) significantly attenuated the antinociceptive effect of beta-endorphin (2.88 nmol, i.t.) in the tail-flick and paw-pressure tests. 4. Both i.t. morphine and DPDPE produced dose-related antinociception in the tail-flick and paw-pressure tests. The potency of DPDPE was lower than that of morphine in both tests; however, the effect of DPDPE was weaker in the paw-pressure test. 5. Administration of ovine beta-endorphin1-27 (1.44 nmol, i.t.) significantly attenuated the antinociceptive effect of morphine (14.9 nmol, i.t.) in both tests and the effect of DPDPE (38.7 nmol) in the tail-flick test. 6. The results show that beta-endorphin1-27 acts as an opioid antagonist at the spinal level in the rat. Its ability to inhibit the action of morphine and DPDPE suggests that it may attenuate beta-endorphin action by an interaction with mu- and/or delta-opioid receptors.