Analgesic effect of nudicauline and its mechanism

Yongping LIU; Jiming TONG

ABSTRACT

BACKGROUND:

One function of papaver nudicaule L is its analgesic effect. Previous studies showed that total alkaloid,extracted from papaver nudicaule,possesses observable analgesic effects. Nudicauline,separated from the total alkaloid of papaver nudicaule,is a new kind of alkaloid.

OBJECTIVE:

To study the analgesic effect of nudicauline and its mechanism of action.

DESIGN:

A randomized controlled study based on the experimental animals.

SETTING:

Institute of Traditional Chinese Medicine ,Chengde Medical Colege.MATERIALSThe experiment was conducted in the Institute of Traditional Chinese Medicine of Chengde Medical College (Key Laboratory for Research and Exploitation of Traditional Chinese Medicine) from August 2001 to December 2003.Totally 140 mice were included and randomly divided into 14 groups with 10 mice in each group in this experiment.

METHODS:

① Study of the analgesic effect.The animals were randomly assigned to 5 groupssaline control group,and nudicauline 2.5,5.0 and 10.0 mg/kg groups as well as morphine group. ② relation with endor-phin.The animals were divided into 5 groupssaline control group,nudicauline +naloxone group,morphine group,and morphine +naloxone group. ③relation with nitrogen monoxide.The animals were divided into 4 groupssaline group,nudicauline group,nudicauline +L-arginine 400 mg/kg group,and n-nitro-L-arginine methyl ester (L-NAME) 37.5 mg/kg group.Totally 20 μL 10 g/L formalin was injected into the right hindlimbs of the mice. The pain observation itemwalking freely was 0 point;being lame,could stand on the floor without moving was 1 point;could lift their feet was 2 point;could shake or lick their feet was 3 points.The observation fell into 2 phases0 to 10 minutes after pain induction was set as the first phase,and 20 to 30minutes was set as the second phase.MAIN OUTCOME

MEASURES:

The pain response scores of the mice in each group under the effect of different drugs.

RESULTS:

① Nudicauline reduced significantly the score of response to the pain induced by formalin in the second phase(P ＜ 0.05-0.01).The higher dosage of nudicauine had certain inhibitory effect on the pain reaction in the first phase (P ＜ 0.05).Morphine had significant inhibitory effect on the pain reaction in both phases(P ＜ 0.01). ② Naloxone could completely inhibit the analgesic effect of morphine,but had no influence on the analgesic effect of nudicauline. ③ The analgesic effect of nudicauline was partially blocked by L-arginine in the second phase and enhanced by L-NAME.

CONCLUSION:

Nudicauline has obvious analgesic effects,whereas opium antagonist naloxone can completely inhibit the analgesic effect of morphine,but cannot alter the effect of nudicauline,which indicates that the analgesic effect is not related to the endogenous opioid system. L-arginine can partially inhibit the analgesic effect of nudicauline while L-NAME can increase the analgesic effect of nudicauline,suggesting that the analgesic effect of nudicauline may be partially associated with the production and release of nitrogen monoxide.