Spinal effects of four injectable anaesthetics on nociceptive reflexes in rats: a comparison of electrophysiological and behavioural measurements

Abstract

1 To assess the direct spinal contributions to the depression of reflexes caused by general anaesthetics, the intravenous potency of four injectable anaesthetics has been compared in two preparations: in decerebrate, spinalised rats, using a novel preparation requiring little surgical intervention, and in intact rats with chronically implanted i.v. cannulae. 2 Methohexitone (1-8mgkg' i.v.), alphaxalone/alphadolone (0.5-8mgkg-' i.v.), alpha-chloralose (20-80mgkg-1 i.v.) and ketamine (0.5-16mgkg-1 i.v.) all produced a dose-dependent depression of single motor unit activity evoked by controlled noxious mechanical stimuli in decerebrate, spinalised animals. 3 The sedative and motor effects brought about by equivalent doses to those used in the electrophysiological experiments were assessed in intact rats. Methohexitone, alphaxalone/alphadolone and alphachloralose all caused similar levels of behavioural sedation at the doses that caused depression of spinal reflexes. Ketamine required relatively much higher doses to cause sedation. 4 To determine whether background anaesthesia modulated the potency with which these compounds affected spinal reflex activity, depressant effects in decerebrate, unanaesthetized rats were compared with those in animals maintained under anaesthesia with either alpha-chloralose or the steroid mixture of alphaxalone/alphadolone. The presence of either of these two agents as maintenance anaesthetics did not influence the effectiveness with which other compounds depressed nociceptive responses. However, additional doses of the maintenance anaesthetics were less effective than the same doses tested in decerebrate animals. 5 All the anaesthetics tested produced a significant depression of spinal reflex responses to noxious stimuli at doses well below those required for anaesthesia. Whilst the presence of maintenance anaesthetics appears not to distort pharmacological tests of other agents, there may nonetheless be a biasing of the samples of cells recorded.

Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

“…Due to advantages like non-invasiveness, relative reproducibility and a good correlation between muscle response and subjective pain intensity in humans, the quantitative assessment of the NWR has become an important tool in pain research (ArendtNielsen and Petersen-Felix, 1995). Our results are consistent with studies in rats and cats that clearly have shown that ketamine selectively reduces spinal reflexes to noxious stimuli (Hartell and Headley, 1990;Headley et al, 1987). They report the inhibition of spinal responses to be dose-dependent.…”

The Periaqueductal Gray Orchestrates Sensory and Motor Circuits at Multiple Levels of the Neuraxis

“…Three additional cycles of pinch stimulation were then repeated to monitor recovery from any descending influences. Only the last 10 s of each response to noxious pinch was analyzed because the initial 5 s was presumed to contain a considerable amount of low-threshold, rapidly adapting activity (Hartell and Headley, 1990). In this and previous studies (McMullan and Lumb, 2006b;Leith et al, 2010), consistency of responses indicate that repeated noxious stimuli (limited to 7 stimuli per animal) at 5 min intervals does not result in tissue damage and/or hyperalgesia.…”

Functional evidence for multiple receptor activation by κ‐ligands in the inhibition of spinal nociceptive reflexes in the rat

“…The preparation of rats for reflex recording has been described previously in detail (Hartell & Headley, 1990;. Briefly, male Wistar rats weighing 300-390 g were anaesthetized with halothane in 02 and the trachea, right carotid and right jugular vein were cannulated.…”