The A1 receptor agonist GR79236 reduces trigeminal Fos expression

Objectives: The adenosine A1 receptor agonist GR79236 (GlaxoSmithKline, UK) has been shown to have antinociceptive and anti-inflammatory properties in animal models (Clayton et al., Br J Pharmacol, 129:75P, 2000). We have previously investigated Fos expression after stimulation of normal and inflamed ferret tooth pulps. The aim of this study was to assess the ability of GR79236 to modify central neurone activation in response to both normal and inflamed ferret tooth pulp stimulation. Methods: Six adult ferrets were prepared under anaesthesia (ketamine 25 mg/kg, xylazine 2 mg/kg: i.m.) to allow tooth pulp stimulation, recording from the digastric muscle and i.v. injections at a subsequent experiment. In three animals pulpal inflammation was induced, by introducing human caries into a deep buccal cavity. Five days later animals were re-anaesthetised (alphaxalone/alphadalone, induction: 6 mg/kg, maintenance: 6-8 mg/kg/h i.v.) and animals were treated with GR79236 (0.1 mg/kg i.v.; normal n = 3, inflamed n = 3). The teeth were then stimulated at 10 times the threshold of the jaw-opening reflex (JOR) for 90 minutes. At 120 minutes from the start of the experiment all animals were perfused with fixative and brainstems processed for Fos immunohistochemistry. Results: Stimulation of normal and inflamed tooth pulps induces ipsilateral Fos expression caudally in subnucleus caudalis (Vc) and rostrally in subnucleus oralis (Vo). Preliminary data shows that GR79236 reduces Fos expression in Vc and Vo in both normal and inflamed animals, with the greatest effect in Vc. GR79236 significantly increased the JOR in both normal (P < 0.05) and inflamed animals (P < 0.05). Conclusion: These results suggest that GR79236 reduces the number of trigeminal brainstem neurones activated by electrical tooth pulp stimulation, with the greatest effect seen caudally. Therefore GR79236 may have analgesic efficacy in dental pain. (Supported by GlaxoSmithKline, UK).