Objective

2

To evaluate the analgesic effects of Wenjing Zhitong prescription （WZP） and explore its possible analgesic mechanisms so as to provide experimental basis for research and development of new Chinese medicine.

Method

2

Analgesic effects of WZP were evaluated by observing the writhing latency and number in the writhing models which were induced by oxytocin in rats as well as those induced by acetic acid and prostaglandin E

1

（PGE

1

）， respectively in mice. Effect of WZP on uterine contraction frequency， amplitude and activity were evaluated by observing the oxytocin-induced contraction of uterine smooth muscle in rats and rabbits

in vivo

. In the oxytocin-induced rat writhing models， the content of prostaglandin F

2

α

（PGF

2

α

） and prostaglandin E

2

（PGE

2

） in rat uterine tissues and the content of beta-endorphins （

β

-EP） in rat serum were detected by enzyme-linked immunosorbent assay （ELISA）. Expression of estrogen receptor （ER） and oxytocin receptor （OTR） in rat uterine were tested by Real-time polymerase chain reaction（Real-time PCR） method to investigate the possible molecular mechanism of WZP for its analgesic effect.

Result

2

Results of analgesic effect showed that in oxytocin-induced rat writhing experiment， the number of writhing responses in both the WZP （1.5，3.0 g·kg

-1

） group was lower than than in the model group （

P

<

0.05）. In acetic acid-induced mice writhing experiment， the latency of writhing response in WZP （6.0 g·kg

-1

） group was significantly prolonged as compared with that in model group

（P

<

0.01）， and the number of writhing response was significantly reduced （

P

<

0.05）. In PGE

1

-induced mice writhing model， the writhing number in WZP （1.5，3.0，6.0 g·kg

-1

） groups was significantly lower than that in the model group （

P

<

0.05，

P

<

0.01）. Results of effect on uterine smooth muscle demonstrated that WZP （0.38，0.75，1.50 g·kg

-1

） could significantly reduce the frequency of uterine smooth muscle contraction in rabbits （

P

<

0.05，

P

<

0.01）， WZP （0.75，1.50，3.00 g·kg

-1

） could significantly reduce the contractile amplitude and activity of smooth muscle in the uterus of rats （

P

<

0.05）. Results of molecular mechanisms of analgesic effects showed that the WZP （0.75，1.50，3.00 g·kg

-1

） significantly reduced the content of PGF

2

α

and the ratio of PGF

2

α

to PGE

2

in the uterine tissue of rats （

P

<

0.01）. In the WZP （3.00 g·kg

-1

） group， the levels of

β

-EP in the serum of rats were significantly increased （

P

<

0.01）， and the levels of OTR in uterus of rats in the WZP （1.50，3.00 g·kg

-1

） group were significantly decreased （

P

<

0.05）.

Conclusion

2

Pharmacological studies demonstrated potent analgesic effect of WZP， and such analgesic effect were mediated by significantly inhibiting contraction of uterine smooth muscle， decreasing the contents of PGF

2

α

and ratio of PGF

2

α

/PGE

2

， reducing OTR expression in uterine as well as increasing the amount of

β

-EP in serum.