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On the selectivity of intravenous p-and K-opioids between nociceptive and non-nociceptive reflexes in the spinalized rat 1

1 In electrophysiological experiments in spinalized, a-chloralose anaesthetized rats, opioids and anaesthetics were tested intravenously (i.v.) on the responses of individual motoneurones to alternating noxious (heat or pinch) and non-noxious (tap or vibration) stimuli. 2 On cells that were sensitive to low doses of y-opioids, both fentanyl (0.5-4pgkg-' i.v.) and morphine (0.5mgkg I i.v.) selectivity reduced reflexes to noxious stimuli to a greater degree than reflexes to non-noxious stimuli. In contrast, on cells that were relatively resistant to these agonists, the higher doses required to reduce nociceptive reflexes (fentanyl 8pgkg-1 i.v.; morphine 18 mg kg-1 i.v.) depressed non-nociceptive reflexes to a similar degree. 3 A similar spectrum of selectivity was seen with U-50,488 (0.5-16mgkg-1 i.v.) although statistically significant selective depression of reflexes was only evident at the lowest dose tested (0.5 mg kg-1 i.v.). All effects of U-50,488 were readily reversed by low doses of the opioid antagonist, naloxone (10-100 yg kg-I i.v.). 4 The dissociative anaesthetic/PCP ligand ketamine (O.5-4mgkg-1 i.v.) was similar in having selective actions at low doses on sensitive cells but non-selective actions when higher doses were required. In contrast, the general anaesthetics methohexitone (4mgkg-1 i.v.) and alphadolone/ alphaxalone (1 mg kgi.v.) were consistently non-selective between reflexes to noxious and nonnoxious stimuli. a-Chloralose (20-40mgkg-' i.v.) had very little effect on reflexes to any of the synaptic inputs tested. 5 The sensitivity of nociceptive reflexes to depression by opioids and dissociative anaesthetics thus determines the selectivity of these agents between nociceptive and non-nociceptive reflexes. The same is not true for the general anaesthetics tested. 6 Taken together with our previous findings that Kas well as p-agonists reduce thermal and mechanical nociceptive reflexes in parallel, these results indicate a general similarity of spinal pand K-opioid actions in the spinal cord of the rat.