OPIOIDERGIC AND CHOLINERGIC BUT NOT NITRIC OXIDE PATHWAYS ARE INVOLVED IN ANTINOCICEPTIVE ACTIVITY OF VITEX AGNUS-CASTUS ESSENTIAL OIL IN THE ACUTE TRIGEMINAL MODEL OF PAIN IN RAT
Objective: Vitex agnus-castus (VAC) and its essential oil traditionally used to treat many conditions and symptoms such as premenstrual problems,
mastalgia, inflammation, sexual dysfunction and pain. This study was conducted to investigate the analgesic effect of essential oil extracted from VAC
(EOVAC) leaves in acute trigeminal model of nociception in adult male Wistar rats. Furthermore, possible involvements of opioidergic, cholinergic and
L-arginine/NO/cyclic GMP pathway in analgesic activity of EOVAC were investigated.
Methods: The EOVAC was extracted from powdered plant material by hydro-distillation in a Clevenger type apparatus. Acute trigeminal pain was
induced by putting a drop of NaCl 5 M solution (40 Î¼l) on the corneal surface of the eye and the numbers of eye wipes counted during the first 30 seconds.
Results: EOVAC at doses of 100 and 200 mg/kg subcutaneous and morphine 2.5 and 5 mg/kg i.p. produced a significant anti-nociceptive effect in
this model of corneal pain. Naloxone (1 mg/kg i.p.) and atropine (1 mg/kg i.p.), L-arginine (100 and 200 mg/kg i.p.) and methylene blue (5 and
10 mg/kg i.p.) alone had no any effect in the acute corneal pain. Pretreatment with naloxone or atropine significantly reversed the EOVACâ€‘induced
analgesia, but L-arginine (300 mg/kg) and methylene blue (5 mg/kg) did not change the suppressive effect of EOVAC on pain response.
Conclusion: The present results suggest that the EOVAC produced anti-nociception in the acute corneal pain through mechanisms that involved both
opioidergic system and/or the cholinergic system, but not via L-arginine/NO/cyclic GMP pathway, supporting the folkloric usage of the plant to treat
various painful processes.
Keywords: Acute trigeminal pain, Vitex agnus-castus essential oil, Opioidergic system, Cholinergic system, Rat.
2. Belmonte C, Acosta MC, Gallar J. Neural basis of sensation in intact and injured corneas. Exp Eye Res 2004;78(3):513-25.
3. Miranda HF, Sierralta F, Prieto JC. Synergism between NSAIDs in the orofacial formalin test in mice. Pharmacol Biochem Behav 2009;92(2):314-8.
4. Petrovic S, Dobric S, Mimica-Dukic N, Simin N, Kukic J, Niketic M. The antiinflammatory, gastroprotective and antioxidant activities of Hieracium gymnocephalum extract. Phytother Res 2008;22(11):1548â€‘51.
5. Zdunic G, Godevac D, Milenkovic M, Vucicevic D, Savikin K, Menkovic N, et al. Evaluation of Hypericum perforatum oil extracts for an antiinflammatory and gastroprotective activity in rats. Phytother Res 2009;23(11):1559-64.
6. Christaki E, Bonos E, Giannenas I, Florou-Paneri P. Aromatic plants as a source of bioactive compounds. Agriculture 2012;2:228-43.
7. Stojkovic D, Sokovic M, Glamoclija J, Dzamic A, Ciric A, Ristic M, GrubiÅ¡ic D. Chemical composition and antimicrobial activity of Vitex agnus-castus L. fruits and leaves essential oils. Food Chem 2011;128:1017-22.
8. Upton R. Chaste Tree Fruit, Vitex Agnus-Castus: Standards of Analysis, Quality Control, and Therapeutics, Santa Cruz, CA: American Herbal Pharmacopoeia; 2001. p. 13-31.
9. Saberi M, Rezvanizadeh A, Bakhtiarian A. The antiepileptic activity of Vitex agnus castus extract on amygdala kindled seizures in male rats. Neurosci Lett 2008;441(2):193-6.
10. Daniel AN, Sartoretto SM, Schmidt G, Caparroz-Assef SM, Bersani-Amado CA, Cuman RK. Anti-inflammatory and antinociceptive activities A of eugenol essential oil in experimental animal models. Rev Bras Farmacognosia 2009;19:212-7.
11. Nasri S, Ebrahimi S. Medical effect of Vitex agnus-castus. J Babol Uni med Sci 2006;7:49-53.
12. Ramezani M, Amin GH, Jalili E. Antinociceptive and anti-inflammatory effects of hydroalcohol extract of Vitex agnus castus fruit. World Acad Sci Eng Technol 2010;64:619-21.
13. do Amaral JF, Silva MI, Neto MR, Neto PF, Moura BA, de Melo CT, et al. Antinociceptive effect of the monoterpene R-(+)-limonene in mice. Biol Pharm Bull 2007;30(7):1217-20.
14. Santos FA, Rao VS. Antiinflammatory and antinociceptive effects of 1,8-cineole a terpenoid oxide present in many plant essential oils. Phytother Res 2000;14:240-4.
15. Choudhary MI, Azizuddin, Jalil S, Nawaz SA, Khan KM, Tareen RB, et al. Antiinflammatory and lipoxygenase inhibitory compounds from Vitex agnus-castus. Phytother Res 2009;23(9):1336-9.
16. Das S, Kanodia L. Effect of ethanolic extract of leaves of Vitex negundo L. on acetic acid induced colitis in albino rats. Asian J Pharm Clin Res 2013;6(3):138-41.
17. Dugoua JJ, Seely D, Perri D, Koren G, Mills E. Safety and efficacy of chastetree (Vitex agnus-castus) during pregnancy and lactation. Can J Clin Pharmacol 2008;15(1):e74-9.
18. Ohyama K, Akaike T, Hirobe C, Yamakawa T. Cytotoxicity and apoptotic inducibility of Vitex agnus-castus fruit extract in cultured human normal and cancer cells and effect on growth. Biol Pharm Bull 2003;26(1):10-8.
19. Prilepskaya VN, Ledina AV, Tagiyeva AV, Revazova FS. Vitex agnus castus: Successful treatment of moderate to severe premenstrual syndrome. Maturitas 2006;55:55-63.
20. Schellenberg R. Treatment for the premenstrual syndrome with agnus castus fruit extract: Prospective, randomised, placebo controlled study. BMJ 2001;322(7279):134-7.
21. Atmaca M, Kumru S, Tezcan E. Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder. Hum Psychopharmacol 2003;18(3):191-5.
22. Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain 1983;16(2):109-10.
23. Farazifard R, Kiani R, Noorbakhsh M, Esteky H. Effects of neonatal C-fiber depletion on the integration of paired-whisker inputs in rat barrel cortex. Exp Brain Res 2005;162(1):115-21.
24. Tamaddonfard E, Khalilzadeh E, Hamzeh-Gooshchi N, Seiednejhad-Yamchi S. Central effect of histamine in a rat model of acute trigeminal pain. Pharmacol Rep 2008;60(2):219-24.
25. Carstens E, Kuenzler N, Handwerker HO. Activation of neurons in rat trigeminal subnucleus caudalis by different irritant chemicals applied to oral or ocular mucosa. J Neurophysiol 1998;80(2):465-92.
26. Hirata H, Meng ID. Cold-sensitive corneal afferents respond to a variety of ocular stimuli central to tear production: Implications for dry eye disease. Invest Ophthalmol Vis Sci 2010;51(8):3969-76.
27. Pan Z, Wang Z, Yang H, Zhang F, Reinach PS. TRPV1 activation is required for hypertonicity-stimulated inflammatory cytokine release in human corneal epithelial cells. Invest Ophthalmol Vis Sci 2011;52(1):485â€‘93.
28. Jones PG, Dunlop J. Targeting the cholinergic system as a therapeutic strategy for the treatment of pain. Neuropharmacology 2007;53(2):197â€‘206.
29. Lima DF, BrandÃ£o MS, Moura JB, LeitÃ£o JM, Carvalho FA, MiÃºra LM, et al. Antinociceptive activity of the monoterpene a-phellandrene in rodents: Possible mechanisms of action. J Pharm Pharmacol 2012;64(2):283-92.
30. Peana AT, Dâ€™Aquila PS, Chessa ML, Moretti MD, Serra G, Pippia P. (-)-Linalool produces antinociception in two experimental models of pain. Eur J Pharmacol 2003;460(1):37-41.
31. Webster DE, He Y, Chen SN, Pauli GF, Farnsworth NR, Wang ZJ. Opioidergic mechanisms underlying the actions of Vitex agnus-castus L. Biochem Pharmacol 2011;81(1):170-7.
32. Samochowiec L, Glaesmer R, Samochowiec J. Einfluss von monchspfeffer auf die konzentration von beta-endorphine im serum weiblicher ratten. Ã„rztez Naturheilverfahren 1998;39:213-5.
33. Ambrosini A, Di Lorenzo C, Coppola G, Pierelli F. Use of Vitex agnus-castus in migrainous women with premenstrual syndrome: An open-label clinical observation. Acta Neurol Belg 2013;113(1):25-9.
34. Buchbauer G, Jirovetz L, JÃ¤ger W, Plank C, Dietrich H. Fragrance compounds and essential oils with sedative effects upon inhalation. J Pharm Sci 1993;82(6):660-4.
35. GuimarÃ£es AG, Quintans JS, Quintans LJ Jr. Monoterpenes with analgesic activity â€“ A systematic review. Phytother Res 2013;27:1-15.
36. Yao QS, Chiou GC. Inhibition of crystallins-induced inflammation in rabbit eyes with five phytogenic compounds. Zhongguo Yao Li Xue Bao 1993;14(1):13-7.
37. Gertsch J, Leonti M, Raduner S, Racz I, Chen JZ, Xie XQ, et al. Beta-caryophyllene is a dietary cannabinoid. Proc Natl Acad Sci U S A 2008;105(26):9099-104.
38. Anand P, Whiteside G, Fowler CJ, Hohmann AG. Targeting CB2 receptors and the endocannabinoid system for the treatment of pain. Brain Res Rev 2009;60(1):255-66.
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