Objective:To analyze the activation of sonic hedgehog(Shh)signaling pathways in the rat model of neuropathic pain and the dynamic changing regularity over time

and to explore the role of Shh in the neuropathic pain. Methods:Eighty adult male SD rats were randomly allocated into two groups(n =40):chronic constriction injury of the sciatic nerve(CCI) group and sham-operated group. Right sciatic nerve was ligated by 4.0 silk suture in CCI group; rats in sham-operated group did not receive ligation and their left sciatic nerves were exposed. General behavior of the two groups were observed respectively to determine mechanical withdrawal threshold(MWT)in rats on 1

4

7

14

28 d after modeling. The expression of Shh

Gli in the spinal cord of the rat lumbosacral enlargement was analyzed using Western blot and immunohistochemistry. Results:The difference in preoperative MWT between CCI group and sham group rats was not statistical significant(P=0.832);MWT was significantly lower at all other time points after the operation(P<0.01). The MWT of CCI group began to decrease on the postoperative first day(P=0.002)

then achieved a minimum on day 7(P=0.027)

and was still in lower level on day 28(P=0.003). The protein expression of Shh

Gli in CCI group rats was not significantly changed on the postoperative first day(P=0.215)

and Shh

Gli in the CCI group were significantly increased at all other time points(P<0.01). The protein expression of Shh

Gli in the CCI group was unregulated on day 7 after injury with maximal expression levels(P<0.01)

which was maintained up to at least day 28 after injury(P<0.01). Immunohistochemistry showed that the Shh and Gli protein displayed significantly increase in the corresponding region than the sham group on the postoperative day 7(P<0.01).Conclusion:Neuropathic pain can induce the expression of Shh signaling pathways. The expressions of related proteins reach the peak on day 7 and maintain the high level till day 28.