title: The effects of ibuprofen and the neurokinin-1 receptor antagonist GR205171A on Fos expression in the ferret trigeminal nucleus following tooth pulp stimulation.
abstract: 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.
authors: Department of Oral and Maxillofacial Medicine and Surgery, School of Clinical Dentistry, Claremont Crescent, University of Sheffield, Sheffield, South Yorkshire S10 2TA, United Kingdom. m.worsley@sheffield.ac.uk
authors: Matthew A
authors: MA
authors: Worsley
authors: Nick M
authors: NM
authors: Clayton
authors: Chas
authors: C
authors: Bountra
authors: Fiona M
authors: FM
authors: Boissonade
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D003481:Cuspid; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D003782:Dental Pulp / Q000294:innervation*; D004353:Drug Evaluation, Preclinical; D004558:Electric Stimulation; D005289:Ferrets; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D007052:Ibuprofen / Q000494:pharmacology* / Q000627:therapeutic use; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D011671:Pulpitis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014277:Trigeminal Neuralgia / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D014278:Trigeminal Nuclei / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D009419:Nerve Tissue Proteins; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D018040:Receptors, Neurokinin-1; C496429:substance P (6-11), Tyr(6)-D-Phe(7)-D-His(9)-; D013373:Substance P; D007052:Ibuprofen