The aim of this study was to develop a rat model of capsaicin-induced pain in the orofacial region. We examined the effects of subcutaneous injection of different doses of capsaicin (0.25, 0.4. 0.8, 1.5, 2.5. 25. 50. 100, 500 mug) on the face-grooming response. Injection of capsaicin into the vibrissa pad produced an immediate grooming of the injected area with ipsilateral fore- or hindpaw. A positive relationship between the amplitude of (lie grooming response and the capsaicin dose was observed until 1.5 V,a, but with the highest concentrations (ranging from 25 to 500 mug) the amplitude of the response decreased. Morphine administered either systemically (in the neck, 0.5-4.0 mg/ka) or locally (0.25-1.0 mg/kg) reduced in a dose-dependent fashion the face grooming provoked by subcutaneous capsaicin (1.5 mug). The systemic and local morphine effects could be reversed by systemic (10.1 mg/kg) and local (0.05 mg/kg) administration of naloxone, respectively. The local administration of morphine (ED50: 0,65 mg/kg) was more potent than systemic injection (ED50: 2.54 mg/ kg) in reducing the grooming behavior. In conclusion, the orofacial capsaicin test appears to be a valid and reliable method for studying trigeminal pain mechanisms and testing analgesic drugs. The results of the present study also support the clinical use of peripheral opioid administration for the treatment of orofacial painful conditions. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.