Spinal antinociceptive actions of mu- and kappa-opioids: the importance of stimulus intensity in determining 'selectivity' between reflexes to different modalities of noxious stimulus

Abstract

1. In electrophysiological experiments in spinalized rats, mu- and kappa-opioids were tested intravenously on the responses of single motoneurones to electronically controlled, alternating noxious heat and noxious pinch stimuli. The effects of mu- and kappa-opioids were compared with those of the general anaesthetic alpha-chloralose and the dissociative anaesthetic/PCP ligand ketamine. 2. The kappa-opioids U-50,488 (0.5-16 mgkg-1 i.v.) and tifluadom (0.05-1.6 mgkg-1 i.v.) had very similar actions to the mu-opioid fentanyl (0.5-16 micrograms kg-1 i.v.). Thus all three agonists reduced thermal and mechanical nociceptive reflexes in parallel and in a dose-dependent manner, but only so long as neuronal responses to the alternating stimuli elicited similar excitability levels in the neurone under study. Ketamine (0.5-16 mgkg-1 i.v.) had similar actions to the opioids whereas alpha-chloralose (20 mgkg-1 i.v.) had very little effect on neuronal responsiveness. 3. Apparently 'selective' depressions by both mu- and kappa-opioids could be orchestrated by a deliberate mismatch of the intensities of alternating noxious heat and pinch stimuli; as measured by neuronal firing rate, the weaker of the responses to either type of stimulus was invariably reduced to a greater degree. 4. Similar 'selectivity' could be demonstrated for both mu- and kappa-ligands when the weaker and stronger responses were of the same modality, being applied by the same pincher device but with alternating applied force. 5. It is concluded that the 'selective' spinal actions of kappa-opioids seen in non-thermal over thermal behavioural models of nociception is likely to be related to the relative intensities, rather than the modalities, of the noxious stimuli used. The validity of the interpretation of results obtained in such behavioural studies is discussed.