Effects of selective and non-selective kappa-opioid receptor agonists on cutaneous C-fibre-evoked responses of rat dorsal horn neurones.

We have studied the effects of 3 putative kappa-opioid receptor agonists, U50488H, ethylketocyclazocine (EKC) and dynorphin A1-13 (DYN) on the processing of nociceptive information in the dorsal horn of the rat under halothane anaesthesia. Extracellular single unit recordings were made from convergent or multireceptive lumbar dorsal horn neurones, which could be excited by impulses in A beta and C fibre afferents following transcutaneous electrical stimulation of their ipsilateral hind paw receptive fields and also by noxious and innocuous natural stimuli. Agonists were applied directly onto the surface of the spinal cord. DYN and U50488H consistently produced both a facilitation and inhibition of the C-fibre evoked nociceptive responses of individual cells, these dual effects being relatively insensitive to naloxone antagonism and cancelled each other for the whole population of cells. A beta fibre-evoked responses were little altered. In contrast, EKC consistently depressed C-fibre transmission in a dose-dependent, naloxone reversible manner, analogous to, but considerably less potent than intrathecal morphine under identical experimental conditions. Agonist-induced effects on neuronal responses to natural stimulation (noxious pinch and innocuous prod) were consistent with the changes observed with the electrically evoked responses. The present results therefore indicate that EKC probably exerts its spinal antinociceptive activity in the rat spinal cord in a manner akin to mu-receptor activation. Results with U50488H and DYN indicate that -opioids can excite and inhibit individual neurones but produce no overall change on the whole population, so differing from effects mediated by the other opiate receptors.