Relationship between spinal Sonic Hedgehog signaling pathway and inflammatory responses in rats with neuropathic pain

Objective To evaluate the relationship between spinal Sonic hedgehog(Shh) signaling pathway and inflammatory responses in rats with neuropathic pain(NP). Methods Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 250-300 g, were divided into 4 groups(n=12 each) using a random number table method: sham operation group(group S), group NP, dimethyl sulfoxide(DMSO) group(group D) and specific Shh signaling pathway inhibitor cyclopamine group(group CP). Spared nerve injury was produced by exposing the sciatic nerve and branches followed by ligation and transection of tibial and common fibular nerves in anesthetized rats. The mechanical paw withdrawal threshold(MWT) was measured at 1 day before establishing the model and 1 and 7 days after establishing the model., The animals were sacrificed after measurement of pain threshold at 7 days after operation, and the lumbar segment L4-6 of the spinal cord was obtained for determination of the expression of Shh, Patched homolog(Ptch), Smoothened(Smo) and zinc finger-containing transcription factors 1(Gli1)(by Western blot) and contents of tumor necrosis factor-alpha(TNF-α) and interleukin-1beta(IL-1β)(by enzyme-linked immunosorbent assay). Results Compared with group S, the MWT was significantly decreased, the expression of Shh, Patched, Smo and Gli1 was up-regulated, and the contents of TNF-α and IL-1β were increased in NP, D and CP groups(P<0.05). Compared with group NP, the MWT was significantly increased, the expression of Shh, Patched, Smo and Gli1 was down-regulated, and the contents of TNF-α and IL-1β were decreased in group CP(P<0.05), and no significant change was found in the parameters mentioned above in group D(P<0.05). Conclusion The mechanism by which Shh signaling pathway is involved in the development and maintenance of inflammatory responses is related to inhibiting inflammatory responses of the spinal cord in rats with NP. Key words: Neuralgia; Hedgehog proteins; Signal transduction; Inflammation; Spinal cord