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Inhibition of spinal opioid antinociception by intrathecal β‐endorphin1–27 in the rat

1 The effects of intrathecal (i.t.) administration of β‐endorphin and two shorter fragments, human and ovine β‐endorphin1–27, were examined for antinociceptive activity in the tail‐flick and paw‐pressure tests in the rat. Additionally, the ability of ovine β‐endorphin1–27 to influence the action of i.t. β‐endorphin, morphine and [d‐Pen2‐d‐Pen5]enkephalin (DPDPE) was also examined in these tests. 2 After i.t. injection, β‐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 β‐endorphin > human β‐endorphin1_27 > ovine β‐endorphin1–27. 3 Administration of ovine β‐endorphin1–27 (0.72, 1.44 nmol, i.t.) significantly attenuated the antinociceptive effect of β‐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 β‐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 β‐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 β‐endorphin action by an interaction with μ‐ and/or δ‐opioid receptors.