Abstract: Objective To explore the effect of inhibiting SHH signaling pathway on the change of hyperalgesia and the change of the BDNF, NR2B level in spinal cord of spared nerve injury rats. Methods Rats were randomly divided into Sham operation group (control group), Spared nerve injury group (SNI group), Solvent group group(SNI-vehicle group) and inhibitor group (SNI-CP group) (n=12). Adopt the method of sciatic nerve branch selective damage to make neuropathic pain models. Pain behavior was assessed and mechanical pain threshold(PMWT) was measured at 1d before operation and the 1, 7 d after SNI operation. After 7 d, animals were then sacrificed and the lumbar segement (L4-6) of the spinal cord was obtained. The expression of SHH, GLI1 and BDNF was detected by Western blotting and Quantitative Real-time PCR method, and the expression of NR2B in the spinal cord was detected by immunohistochemistry method. Results Compared with control group, after the SNI operation in SNI group, SNI-vehicle group and SNI-CP group PMWT was significantly decreased, the protein and mRNA expression of SHH, GLI1 and BDNF were obviously increased, the protein expression of NR2B were obviously increased(P＜0.05). Compared with SNI group, PMWT was significantly increased in SNI-CP group, the the protein and mRNA expression of SHH, GLI1 and BDNF were partly decreased, the protein expression of NR2B were partly decreased(P＜0.05). Conclusions Inhibition of SHH signaling pathway can alleviate neuropathic pain in SNI rats and its mechanism may be related to the regulation of BDNF, NR2B in the spinal cord level.

Key words: 【Key words】SHH signaling pathway, cyclopamine, neuropathic pain, BDNF, NR2B