A Rabbit Model for the Evaluation of Epidurally Administered Local Anaesthetic Agents

Abstract

A rabbit model is described for the evaluation of epidurally administered local anaesthetic agents. The technique involves a single injection via the readily identified lumbosacral space in conscious rabbits, with the epidural space being identified by a modified loss-of-resistance technique. The endpoints used to assess pharmacodynamic responses of the rabbit model were (I) sensory loss, (2) loss of weight-bearing ability, and (3) flaccid paresis. The model was further characterised by investigation of endpoint responses to changes in injection volume (0.1-0.25 ml/kg) and concentration of administered lignocaine solutions (0.5 to 2%). From these studies, a volume of 0.2 ml/kg was chosen as a standard dose and a subsequent comparison between different agents undertaken. The rank order for the onset of action, duration of effect and the observed pharmacokinetic profiles after epidural administration of 2% lignocaine, 2% lignocaine with adrenaline (1:200,000) or 0.5% bupivacaine solutions are broadly consistent with human clinical data. These data indicate that the rabbit is a simple (albeit limited) model for the screening evaluation of epidurally administered local anaesthetic agents.