| Objective We aim to establish an ideal animal model of paclitaxel induced neuropathic pain. To investigate the preventive and therapeutic effect of tetramethylpyrazine in the rat model of neuropathic pain, and detect the expressions of nerve growth factor(NGF)protein in the central and peripheral nervous system.Methods 15 adult male SD rats were randomly divided into 3 groups,the rats were injected i.p. every other day(day 1、3、5、7) with vehicle or paclitaxel(1.0 or 2.0mg·Kg-1·d-1),the first day of the research is the day when we I.P the drug to the rats first time.Mechanical withdrawal threshold(MWT) and thermal withdrawal latency(TWL)of rats hind paw were measured before 1 day and 3、5、7、12、16 and 20 days after the injection.The sciatic nerve was analyzed by electron microscope at 22 days after the injection;After an ideal animal model of chemotherapy induced neuropathic pain was successively established. 30 adult male SD rats were randomly divided into 4 groups, the rats were injected i.p. every other day with appropriate dosage of paclitaxel(use the right dosage of the animal-model experiment before),A(n=6)group is control group,tetramethylpyrazine injection(200mg/Kg·d,i.p)or pregabalin capsules(3 mg/Kg·d,po.)followed by Paclitaxel for14 days in B( n=8) and C( n=8) group. In D( n=8) group,tetramethylpyrazine injection and pregabalin capsules are all gave by the same method and dosage with B and C group. MWT and TWL of rats hind paw were measured before 1 day and 7、12、16 and 20 days after injection. On 22 days after injection, the sciatic nerve was analyzed by electron microscope and immunohistochemical method was used to detect the expressions of NGF protein in the dorsal horn 、dorsal root ganglion and sciatic nerve.Results In the two paclitaxel groups, MWT and TWL were obvious decreased(p<0.05) from the 5thand 7thday to the end of the experiment,the injury of sciatic nerve was more serious in these two groups,and there is the most serious injury in the 2.0mg·Kg-1·d-1paclitaxel group;In the second experiment,compared with the control group,MWT was obvious increased in tetramethylpyrazine group(p<0.05) from the 12 thday and TWL was obvious increased in tetramethylpyrazine group(p<0.05) from 7thday,the increased continued until the end of the experiment;the tetramethylpyrazine has the same effect with pregabalin, and the two drugs have analgesic effect,compared with the control and pregabalin groups,the increased of MWT and TWL is more obvious in the combined drug group(p<0.05).The injury of sciatic nerve was more serious in control group,the two groups which used tetramethylpyrazine injection have the more slight nerve injury;The expression of NGF in the nerve system was significantly higher in control group,tetramethylpyrazine add pregabalin can reduce the expression of NGF(p<0.05).ConclusionAn ideal animal model of chemotherapy induced neuropathic pain was successively established by injected i.p.2.0mg/·Kg-1·d-1paclitaxel on 4 alternate days(every other day,day 1、3、5、7)in SD male rats;Tetramethylpyrazine injecion can effective prevention and treatment the paclitaxel-induced neuropathic pain,the effect is similar with pregabalin and it has synergistic effects with pregabalin;It also can alleviate the injury of peripheral nerve( sciatic nerve);the therapeutic mechanism is may be related with the lower expression of NGF in the nervous system(tetramethylpyrazine can reduce the NGF’s expression of the central and peripheral nervous system). |
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