Effect Of Inhibiting Sonic Hedgehog Signaling Pathway In Spinal Cord On Neuropathy Pain Rats And Its Possible Mechanism

Objective To explore how the activation and inhibition of Shh signaling pathway to effect on the hyperalgesia, the proliferation of astrocytes and the expression of BDNF and NR2B in the spinal cord level of neuropathic pain rats.Methods Ninety-six male SD rats were randomly divided into 4 groups (n=24):Sham operation group (control group), Spared nerve injury group (SNI group), Solvent group (SNI-vehicle group) and inhibitor group (SNI-CP group). Pain behavior was assessed and mechanical pain threshold (MWT) was measured at Id before operation and the 1 and 7 d after SNI operation. After behavioral and MWT detection of 7 d, animals were then sacrificed and the lumbar segement (L4-6) of the spinal cord was obtained. The protein expression of Shh, Ptch, Smo, Gli1, GFAP, BDNF and NR2B was determinated by Western blotting, the mRNA expression of Shh, Ptch, Smo, Gli1, BDNF and NR2B was determinated by Quantitative Real-time PCR method, and the expression of Shh and GFAP in the spinal cord was located by immunofluorescence method.Results Compared with control group, the behavior of limp, toe deformity, licking, biting and jitter of parapodum autophagy appeared at 1 d after operation in SNI group, SNI-vehicle group and SNI-CP group, the MWT was significantly decreased at 1 d and 7 d after operation (P<0.05), the protein and mRNA expression of Shh, Ptch, Smo, Gli1, BDNF, NR2B and the protein expression of GFAP were obviously increased (P<0.05). Compared with SNI group and SNI-vehicle group, MWT was significantly increased in SNI-CP group at 7 d after operation(P<.05), the the protein and mRNA expression of Shh, Ptch, Smo, Gli1, BDNF, NR2B and the protein expression of GFAP were partly decreased (P<0.05). Immunofluorescence localization found:Shh is mainly expressed in the gap around astrocytes in spinal dorsal horn.Conclusion Sonic Hedgehog signaling pathway may be involved in the development of neuropathic pain, and inhibiting Shh signaling pathway can improve the pain sensitization in SNI rats. Its mechanism may be related to regulate on the number of mature astrocytes and on the expression of BDNF and NR2B in spinal cord level.