Antagonism of μ-opioid receptor-mediated inhibitions of nociceptive neurones by U50488H and dynorphin A 1–13 in the rat dorsal horn

Abstract

We have studied the effects of two highly selective κ-opioid receptor agonists, U50488H and dynorphin A 1–13 on the powerful inhibitions of rat dorsal horn nociceptive neurones produced by the potent μ-opiate receptor agonist, Tyr- d-Ala-Gly-Me-Phe-Gly-ol (DAGO). Extracellular single unit recordings were made from 35 convergent neurones which could be excited by impulses in Aβ- and C-fibre afferents following transcutaneous electrical stimulation of the ipsilateral hind paw. The μ- and κ-agonists were applied directly onto the surface of the spinal cord. DAGO (0.19, 0.48 and 1.9 nmol) dose-dependently inhibited C-fibre evoked responses with little effect on Aβ-evoked activity. The spinal application of dynorphin A 1–13 (6.2 nmol) and U50488H (28 nmol) rapidly reversed the spinal inhibitory effect of DAGO indicating that these κ-ligands are likely to act as μ-receptor antagonists in the rat dorsal horn.