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

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Abstract
1 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. 2 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. 3 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. 4 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. 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 κ opioids are ineffective in tests of thermal nociception, and secondly to the likely spinal mechanisms by which opioid receptor agonists mediate antinociception.