Trigeminal pain mechanisms: 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 previously investigated Fos expression after stimulation of normal and inflamed ferret tooth pulps. The aim of this study was to compare the effects of ibuprofen (Sigma, UK) and a neurokinin-1 receptor antagonist GR205171A (GlaxoSmithKline, UK) on the excitability of central trigeminal neurones in response to stimulation of normal and inflamed ferret tooth pulp. Nineteen 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 ten animals pulpal inflammation was induced, by introducing human caries into a deep 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 either ibuprofen (111 mg/kg i.v.; normal n = 4 inflamed n = 5) or GR205171A (500 mg/kg i.v.; normal n = 5, inflamed n = 5). The teeth were stimulated at 10 times the threshold of the jaw-opening reflex for 90 minutes. At 120 minutes from the start of the experiment all animals were perfused with fixative and brainstems processed for Fos immunohistochemistry. Stimulation of normal and inflamed tooth pulps induces ipsilateral Fos expression caudally in subnucleus caudalis (Vc) and rostrally in subnucleus oralis (Vo). GR205171A had no effect on Fos expression in Vc (P > 0.05, unpaired t-test) or Vo (P > 0.05) in either normal or inflamed animals. Ibuprofen reduced Fos expression in Vc (P < 0.05), yet had no effect in Vo (P > 0.05) in both normal and inflamed animals. These results suggest that ibuprofen reduces the number of trigeminal brainstem neurones activated by electrical tooth pulp stimulation caudally but not rostrally in all animals. GR205171A does not modify Fos expression in response to tooth pulp stimulation. Supported by GlaxoSmithKline, UK.