Emad Khalilzadeh - Division of Physiology, Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, I.R.Iran.
Gholamreza Vafaei Saiah - Division of Physiology, Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, I.R.Iran.
Hamideh Hasannejad - Division of Physiology, Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, I.R.Iran.
Adel Ghaderi - Division of Physiology, Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, I.R.Iran.

Objective: Vitex agnus-castus (VAC) and its essential oil have been traditionally used to treat many conditions and symptoms such as premenstrual problems, mastalgia, inflammation, sexual dysfunction, and pain. In this study, the effects of essential oil extracted from Vitex agnus-castus (EOVAC) leaves were investigated in three behavioral models of nociception in adult male Wistar rats. Materials and methods: Chemical composition of EOVAC was analyzed using gas chromatography – mass spectrometry (GC-MS) and also its possible toxicity was determined in mice. Analgesic effect of EOVAC was determined using tail immersion test, formalin test, and acetic acid-induced visceral pain in rats. Results: EOVAC (s.c.) and morphine (i.p.) significantly (p<0.05) reduced pain responses in both formalin and tail immersion tests. In the study of evolved mechanisms, pretreatment with naloxone or atropine significantly (p <0.05) reversed the essential oil-induced analgesia in both formalin and tail immersion tests. Moreover, EOVAC and Piroxicam produced significant (p<0.05) inhibition in the acetic acid-induced writhing response.EOVAC did not show any mortality even at high dose (5 g/kg, p.o.) of administration in toxicity test. Moreover, according to GC-MS results, major components of the EOVAC were α-pinene (14.83%), limonene (10.29%), β-caryophyllene (6.9%), sabinene (5.27%), and β-farnesene (5.9%). Conclusions: These results suggest that endogenous opioidergic system as well as muscarinergic receptors of cholinergic system may be involve in the antinociceptive activity of Vitex agnus-castus essential oil in these models of pain in rats.  

Vitex agnus-castus, Antinociception, acute toxicity, Chemical composition, Rat