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We have developed a model to study central changes following inflammation of the tooth pulp in the ferret and have examined Fos expression in the trigeminal nucleus following stimulation of non-inflamed and inflamed tooth pulps. The aim of this study was to establish the ability of this model to predict analgesic efficacy in clinical studies of inflammatory pain. We addressed this by assessing the effects of the neurokinin-1 receptor antagonist GR205171A and ibuprofen on Fos expression following stimulation of the inflamed pulp and comparing this with known analgesic efficacy. Adult ferrets were prepared under anaesthesia to allow tooth pulp stimulation, recording from the digastric muscle and intravenous injections at a subsequent experiment. In some animals pulpal inflammation was induced, by introducing human caries into a deep buccal cavity. After 5 days, animals were reanaesthetised, treated with vehicle, GR205171A or ibuprofen and the teeth were stimulated at ten times the threshold of the jaw-opening reflex. Stimulation of all tooth pulps induced ipsilateral Fos in trigeminal subnuclei caudalis and oralis. GR205171A had no significant effect on Fos expression in the trigeminal nucleus of animals with either non-inflamed or inflamed tooth pulps. Ibuprofen reduced Fos expression in the trigeminal nucleus and this effect was most marked in animals with pulpal inflammation. These results differ from those previously described using a range of other animal models, but agree with known clinical efficacy of neurokinin-1 receptor antagonists and ibuprofen. Therefore this model is likely to be of use in accurately predicting the analgesic efficacy of novel compounds.

Original publication

DOI

10.1016/j.ejpain.2007.07.010

Type

Journal article

Journal

Eur J Pain

Publication Date

04/2008

Volume

12

Pages

385 - 394

Keywords

Animals, Anti-Inflammatory Agents, Non-Steroidal, Cuspid, Cyclooxygenase Inhibitors, Dental Pulp, Drug Evaluation, Preclinical, Electric Stimulation, Ferrets, Gene Expression Regulation, Genes, fos, Ibuprofen, Nerve Tissue Proteins, Neurokinin-1 Receptor Antagonists, Peptide Fragments, Proto-Oncogene Proteins c-fos, Pulpitis, Receptors, Neurokinin-1, Substance P, Trigeminal Neuralgia, Trigeminal Nuclei