Noxious chemical stimulation of the rat nasal mucosa induces the expression of the immediate early gene c-fos in trigeminal brainstem neurons. In the present study, we applied the irritant mustard oil (1%) into the left nostril of urethane anesthetized rats. Immunohistochemical methods were used to evaluate the expression of Fos protein in the trigeminal subnuclei interpolaris and caudalis and to test the effects of putative analgesics that might depress synaptic transmission in neurons related to nociception. For this purpose, morphine (3 mg/kg and 10 mg/kg), the 5-HT2 antagonist ketanserin (0.5 mg/kg and 5 mg/kg) and the 5-HT3 antagonist ICS 205-930 (0.1 mg/kg and 1 mg/kg) were administered intravenously prior to noxious stimulation. Pretreatment with any of the three compounds reduced Fos-like immunoreactivity. The effect of morphine was reversible with naloxone. The reduction of the expression of Fos-like immunoreactivity by exogenous morphine speaks in favour of an opioidergic link in the modulation of orofacial pain in the trigeminal nuclei. The effects of the 5-HT receptor antagonists are most likely mediated via 5-HT2 and 5-HT3 receptors located on primary afferent fibres.