EFFECTS OF INTRAVENOUS MU AND KAPPA-OPIOID RECEPTOR AGONISTS ON SENSORY RESPONSES OF CONVERGENT NEURONS IN THE DORSAL HORN OF SPINALIZED RATS

1 Electrophysiological experiments have been performed to assess the effects of intravenously administered mu and kappa opioid agonists on the responses to noxious thermal and mechanical and non-noxious tactile stimuli of single convergent neurones in laminae III-VI of the dorsal horn of spinalized rats anaesthetized with alpha-chloralose. 2 The mu receptor agonists tested were fentanyl (1-16-mu-g kg-1) and morphine (0.5-16 mg kg-1) and the kappa-receptor agonists U-50,488 (1-16 mg kg-1) and tifluadom (0.1-1.6 mg kg-1). Multiple drug tests were made on each cell so that compounds could be compared under closely comparable conditions. 3 In one protocol, thermal and mechanical nociceptive responses of matched amplitudes were elicited alternately. Both mu and kappa agonists dose-dependently reduce the neuronal responses. Thermal nociceptive responses were as sensitive to the kappa agents as were the mechanical nociceptive responses; the mu agonists similarly reduced both types of response in parallel. 4 In another protocol, nociceptive and non-nociceptive responses were elicited alternately to permit the degree of selective antinociception to be assessed. The mu agonists were scarcely selective, fentanyl reducing nociceptive only slightly (but significantly at 4-16-mu-g kg-1) more than non-nociceptive responses. The kappa-opioid agonist U50,488 reduced tactile responses somewhat more than nociceptive responses. 5 The spontaneous discharge of these cells with ongoing activity was reduced to a significantly greater degree than the evoked responses; this is likely to have contributed to the non-selectivity of the reduction of the evoked responses. 6 The results are discussed with respect firstly to previous reports that kappa opioids are ineffective in tests of thermal nociception, and secondly to the likely spinal mechanisms by which opioid receptor agonists mediate antinociception.