Methods: Ten adult ferrets were prepared under anaesthesia (ketamine 25mg/kg, xylazine 2mg/kg, IM) to allow tooth pulp stimulation, recording from the digastric muscle and intravenous injections at subsequent experiments. In all of these animals pulpal inflammation was induced by introducing human caries into a deep buccal cavity. Four days later the animals were treated intravenously with either a CGRP antibody (Sigma-Aldrich, 2mg/ml/kg, n=5) or vehicle (phosphate-buffered saline [PBS], 1ml/kg, n=5). Six days after the initial setup the animals were re-anaesthetised (alfaxalone, induction: 4mg/kg, maintenance: 10.5-16mg/kg/h, IV) and the jaw opening reflex (JOR) threshold was measured. The tooth pulps were then stimulated at 10 x JOR threshold for 90 minutes. 120 minutes from the start of the stimulation, animals were perfused with fixative and brainstems processed for Fos immunohistochemistry.
Results: Stimulation of inflamed tooth pulps induced ipsilateral Fos expression in two regions of the trigeminal nucleus, subnucleus caudalis (Vc) and subnucleus oralis (Vo). Fewer Fos-positive nuclei were present within Vc of animals treated with the CGRP antibody (mean 230 ± 45 [SEM] cells) than in those treated with vehicle (mean 451 ± 32 cells; p=0.003). Counts were not significantly different in Vo.
Conclusions: Previous studies using this model have demonstrated that it is able to predict clinical analgesic efficacy. Thus these data indicate that this antibody may have analgesic effects in dental pain and other types of inflammatory mediated transmission.
(Supported by Eli Lilly and the BBSRC).