ABSTRACT
BACKGROUND: It has been considered that Cestrum nocturnum L. (CNL) has the effects of antiarrhythmia, local anesthesia and central inhibition.OBJECTIVE: To investigate the analgesic effect of CNL extract on mice,so as to find new drugs for clinical treatment of pain.DESIGN: A randomized control observation.SETTING: Center of Modern Education and Department of Pharmacology,Gannan Medical College.MATERIALS: The experiments were carried out in the laboratory of scientific research center, Gannan Medical College between March and April in 2005. ① A total of 150 healthy adult Kunming mice were used in four independent experiments. ② Drugs: CNL extract was provided by the Department of Phytochemistry, Shenyang Pharmaceutical University (batch number: 2002080901), morphine hydrochloride injection by Shenyang No.1Pharmaceutical Factory (batch number: 000305), and naloxone hydrochloride injection by Yanqiao (Hunan) Pharmaceutical Co. Ltd., (batch number:20021109).METHODS: ① Effects of CNL extract on writhing times induced by acetic acid: Forty female mice were randomly divided into four groups with10 mice in each, and they were treated with intraperitoneal injections of 0.02 mL/g saline, 0.10 and 0.20 mg/g CNL extract and 0.10 mg/g aminophenazone respectively. The intraperineal injection of 6 g/L glacial acetic acid was given after 15 minutes. The writhing times of mice within 15 minutes were observed and recorded in each group. ② Effects of CNL extract on the pain induced by hot pla in mice: Forty female mice were randomly divided into four groups with 10 mice in each, and they were treated with intraperineal injections of 0.02 mL/g saline, 0. 10 and 0.20 mg/g CNL extract and 0.10 mg/g morphine respectively. The pain responses were detected at 15, 30 and 60 minutes after administration. ③ The antagonistic effect of naloxone on morphine and CNL extract to the pain induced by hot plate in mice: Thirty female mice were randomly divided into three groups ith 10 mice in each group, and they were given intraperitoneal injections of 0.02 mL/g saline, naloxone 0.004 mg/g +morphine 0.01 mg/g and naloxone 0.004 mg/g+CNL extract 0.01 mg/g respectively. The pain responses were detected at 15, 30 and 60 minutes after administration respectively. ④ Effects of CNL extract on electrostimulation induced pain in mice: Forty mice were randomly divided into four groups with 10 mice in ach group, and they were administrated with intraperineal injections of 0.02 mL/g saline, 0.10 and 0.20 mg/g CNL extract and 1 g/L morphine respectively. Repeated electrostimulations were given at 20, 35, 50 and 70minutes after administration, and the pain responses were detected by means of electrostimulation.MAIN OUTCOME MEASURES: ① Writhing times; ② Time for the pain response induced by hot plate; ③ Analgesic rate induced by electrostimulation.RESULTS: Totally 150 healthy adult Kunming mice were used in the four independent experiments, and all were involved in the analysis of results. ①Writhing times in the mice: 0.10 and 0.20 mg/g CNL extracts and 0.10 mg/g aminophenazone had very significant analgesic effects on writhing induced byacetic acid in mice, and the writhing times after administration were all fewer than those in the saline group (20.2±10.8, 14.5±7.6, 7.6±4.5,50.6±15.5, P ＜ 0.01), and the analgesic effects of CNL extract were dosedependently. ② Time for the pain response induced by hot plate: 0.10 and 0.20 mg/g CNL extracts had significant analgesic effects on the pain in duced by hot plate, and the time for pain sensation at 15, 30 and 60 minutes after administration were all longer than those in the saline group (P ＜ 0.05 or P ＜ 0.01), and the analgesic effect was dose-dependently. The times for pain sensation at each time point after administration in the naloxone 0.004 mg/g+CNL extract 0.01 mg/g group were all longer than those in the saline group, but those were close between the naloxone 0.004 mg/g+morphine 0.01 mg/g group and the saline group. ③ Analgesic rate induced by electrostimulation in the mice: The analgesic rates at20, 35, 50 and 70minutes after administration in the CNL extract 0.10 and 0.20 mg/g groups were all higher than those in the saline group (P ＜ 0.01).CONCLUSION: Our data suggested that CNL extract has obvious analgesic effect, and the analgesic intensity is dose-dependently. Naloxone, an opiate receptor antagonist, can antagonize the analgesic effect of morphine,but cannot antagonize that of CNL extract on mice with pain induced by hot plate, which indicates that CNL extract exert its analgesic role not through binding with opiate receptor.