Phytomedicine 15 (2008) 630–634 Antinoceptive effect of triterpenoid a,b-amyrin in rats on orofacial pain induced by formalin and capsaicin S.A. Holanda Pinto a , L.M.S. Pinto a , M.A. Guedes a , G.M.A. Cunha a , M.H. Chaves b , F.A. Santos a , V.S. Rao a,Ã a Department of Physiology and Pharmacology, Post-Graduation Programme in Medical Sciences, Faculty of Medicine, Federal University of Ceara, POB 3157, Rua Cel Nunes de Melo-1127, Porangabussu, 60430-270 Fortaleza, Ceara, Brazil b Department of Organic and Inorganic Chemistry, Federal University of Piaui, Teresina, Piaui, Brazil Abstract The effects of a,b-amyrin, a pentacyclic triterpene isolated from Protium heptaphylum was investigated on rat model of orofacial pain induced by formalin or capsaicin. Rats were pretreated with a,b-amyrin (10, 30, and 100 mg/kg, i.p.), morphine (5 mg/kg, s.c.) or vehicle (3% Tween 80), before formalin (20 ml, 1.5%) or capsaicin (20 ml, 1.5 mg) injection into the right vibrissa. In vehicle-treated controls, formalin induced a biphasic nociceptive face-rubbing behavioral response with an early first phase (0–5 min) and a late second phase (10–20 min) appearance, whereas capsaicin produced an immediate face-rubbing (grooming) behavior that was maximal at 10–20 min. Treatment with a,b-amyrin or morphine significantly inhibited the face-rubbing response in both test models. While morphine produced significant antinociception in both phases of formalin test, a,b-amyrin inhibited only the second phase response, more prominently at 30 mg/kg, in a naloxone-sensitive manner. In contrast, a,b-amyrin produced much greater antinociceptive effect at 100 mg/kg in the capsaicin test, which was also naloxone-sensitive. These results provide first time evidence to show that a,b-amyrin attenuates orofacial pain atleast, in part, through a peripheral opioid mechanism but warrants further detailed study for its utility in painful orofacial pathologies. r 2007 Published by Elsevier GmbH. Keywords: Protium heptaphyllum; a,b-Amyrin; Antinociception; Orofacial pain; Formalin; Capsaicin Introduction Orofacial pain is a common complaint patients seek medical or dental care. Orofacial pain is frequent with a high prevalence in temporomandibular and dental disorders, malignant diseases, and in chemo-radiother- apy-surgery-associated mucositis and neurotoxicity (Benoliel et al., 2007; Epstein et al., 2007). A wide variety of drugs are indicated for treating orofacial pain, which include NSAIDs, muscle relaxants, opioids and antidepressants but side effects and toxicity are apparent with long-term administration (Dionne, 2001). In recent years, there has been a constant search for alternative drugs that possess greater efficacy and safety in reducing the inflammatory and neuropathic pain and with a strategy to halt the transition from acute to pain chronicity. Protium heptaphyllum (Aubl.) March., commonly known as alme´cega, is a widely distributed plant in the Amazon and in Northeast of Brazil. The resin collected from its trunk wood is an effective healing agent of ARTICLE IN PRESS www.elsevier.de/phymed 0944-7113/$ - see front matter r 2007 Published by Elsevier GmbH. doi:10.1016/j.phymed.2007.11.016 Ã Corresponding author. Tel.: +55 85 3366 8341; fax: +55 85 3366 8333. E-mail addresses: vietrao@ufc.br, viet_rao@yahoo.com.br (V.S. Rao).