Effects of intravenous μ and κ opioid receptor agonists on sensory responses of convergent neurones in the dorsal horn of spinalized rats

Abstract

Electrophysiological experiments have been performed to assess the effects of intravenously administered μ and κ 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 α‐chloralose. The μ receptor agonists tested were fentanyl (1–16 μg kg−1) and morphine (0.5–16 mg kg−1) and the κ‐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. In one protocol, thermal and mechanical nociceptive responses of matched amplitudes were elicited alternately. Both μ and κ agonists dose‐dependently reduce the neuronal responses. Thermal nociceptive responses were as sensitive to the κ agents as were the mechanical nociceptive responses; the μ agonists similarly reduced both types of response in parallel. In another protocol, nociceptive and non‐nociceptive responses were elicited alternately to permit the degree of selective antinociception to be assessed. The μ agonists were scarcely selective, fentanyl reducing nociceptive only slightly (but significantly at 4–16 μg kg−1) more than non‐nociceptive responses. The κ‐opioid agonist U50,488 reduced tactile responses somewhat more than nociceptive responses. 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. The results are discussed with respect firstly to previous reports that κ opioids are ineffective in tests of thermal nociception, and secondly to the likely spinal mechanisms by which opioid receptor agonists mediate antinociception. 1991 British Pharmacological Society