Antagonism of mu-opioid receptor-mediated inhibitions of nociceptive neurones by U50488H and dynorphin A1-13 in the rat dorsal horn.

We have studied the effects of two highly selective kappa-opioid receptor agonists, U50488H and dynorphin A1-13 on the powerful inhibitions of rat dorsal horn nociceptive neurones produced by the potent mu-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 A beta- and C-fibre afferents following transcutaneous electrical stimulation of the ipsilateral hind paw. The mu- and kappa-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 A beta-evoked activity. The spinal application of dynorphin A1-13 (6.2 nmol) and U50488H (28 nmol) rapidly reversed the spinal inhibitory effect of DAGO indicating that these kappa-ligands are likely to act as mu-receptor antagonists in the rat dorsal horn.