Methods: Fifteen 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 eight of these 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 the jaw opening reflex (JOR) threshold was measured. Animals were treated with either SB823387 (i.v. bolus: 45 mg/ml/kg, i.v. infusion: 11 mg/2.5ml/kg over 1 h; non-inflamed n = 4, inflamed n = 4) or vehicle (0.9% saline; non-inflamed n = 3, inflamed n = 4). Fifteen minutes after the initial bolus tooth pulp stimulation commenced at 10 times the threshold of the JOR for 90 minutes. All animals were perfused with fixative 120 minutes from the start of the stimulation and brainstems processed for Fos immunohistochemistry.
Results: Stimulation of non-inflamed and inflamed tooth pulps induced ipsilateral Fos expression caudally in subnucleus caudalis (Vc) and rostrally in subnucleus oralis (Vo). SB823387 reduced Fos expression in both Vc (non-inflamed P = 0.001, inflamed P = 0.002, unpaired t-test) and Vo (non-inflamed P = 0.05, inflamed P = 0.009).
Conclusion: These results suggest that SB823387 reduces the number of trigeminal brainstem neurones activated by tooth pulp stimulation. Therefore SB823387 may have analgesic efficacy in dental pain. (Supported by GlaxoSmithKline, UK).