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Introduction: Feverfew (Tanacetum parthenium) (T.p.) is widely used in folk medicine to treat many diseases. We reported the analgesic effect of T.p. flower and leaf previously. Present study is designed to find the mechanism underlying the anti-nociceptive effect of the aqueous extract of T.p. flower. Method: Based on our previous study, the dose 50 mg/kg i.p. of the T.p. aqueous extract had a potent analgesic effect on mice (NMRI) (20 ± 2 g) in formalin test which is used in the present study also. Here, we study the roles of opioidergic, sertoninergic and α - adrenergic systems on the anti-nociceptive effect of the extract. Animals had pretreated with drugs, 15 min before the extract treatments, including opioid antagonist naloxane (5mg/kg, i.p.), sertoninergic antagonist cyproheptadine (4 mg/kg, i.p.) and α-adrenergic antagonist phentolamine (20 mg/kg, i.p.) separately (each group with n≥6). Saline and extract used as controls. Results: In contrast to extract analgesic effect, pretreatment with naloxan increased the pain sensation in the neurogenic phase of formalin test (p<0.001). Pretreatment with cyproheptadine increased the sensation of pain in both early and late phases (p<0.05). Inhibition of α -adrenergic system was not be able to attenuate the anti-nociceptive effect of the extract. Discussion: The involvement of sertoninergic system in anti-nociceptive effect of the T.p. extract is proposed by the results. Also the involvement of opioidergic system has to be mentioned in this effect.

Keywords: Tanacetum parthenium, opioidergic system, sertoninergic system, α -adrenergic system, formalin test, mice

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