On the selectivity of intravenous μ- and κ-opioids between nociceptive and non-nociceptive reflexes in the spinalized rat

Abstract

1. In electrophysiological experiments in spinalized, α-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 μ-opioids, both fentanyl (0.5-4 μg kg-1 i.v.) and morphine (0.5 mg kg-1 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 8 μg kg-1 i.v.; morphine 1-8 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 (0.5-16 mg kg-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 μg kg-1 i.v.). 4. The dissociative anaesthetic/PCP ligand ketamine (0.5-4 mg kg-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 (4 mg kg-1 i.v.) and alphadolone/alphaxalone (1 mg kg-1 i.v.) were consistently non-selective between reflexes to noxious and non-noxious stimuli. α-Chloralose (20-40 mg kg-1 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 κ- as well as μ-agonists reduce thermal and mechanical nociceptive reflexes in parallel, these results indicate a general similarity of spinal μ- and κ-opioid actions in the spinal cord of the rat.