Neuropathic Pain Relieving in Rats by the Inhibition of Monomer of Lamiophlomis Rotata on AKT-mTOR Signaling Pathway in Spinal Dorsal Horn / 中国药师

ABSTRACT

Objective:To observe the effect of intrathecal administration of 8-O-acetyl-SM(8-OaS) on chronic neuropathic pain in rats by inhibiting the expression of protein kinase B(AKT)-mammalian target of rapamycin(mTOR) signaling pathway in spinal dorsal horn after spinal nerve ligation.Methods:The rat model of neuropathic pain was established by lumbar 5 spinal nerve ligation(SNL), and Von Frey filament was used to investigate the mechanical allodynia. Immunofluorescent histochemistry was adopted to investigate the distribution of pAKT and pmTOR in spinal dorsal horn. The protein levels of pAKT and pmTOR in spinal dorsal horn after drug ad-ministration were quantitatively determined by Western blot. Results: Compared with that in the sham group, the paw withdrawal threshold (PWT) significantly decreased(P<0.01),and the intrathecal administration of 8-OaS attenuated mechanical allodynia ob-viously during the first day and the seventh day after the operation(P<0.05). Meanwhile,double immunofluorescent staining showed the co-expression of pAKT and astrocytes marker glial fibrillary acidic protein(GFAP),and positive labeling of pmTOR was expressed in spinal astrocytes and neurons. The results of Western blot revealed that the protein levels of pAKT and pmTOR in spinal dorsal horn were significantly reduced after the treatment of 8-OaS. Conclusion:Intrathecal administration of 8-OaS attenuates the PWT of SNL-in-duced chronic neuropathic pain. The underlying mechanism of the potential anti-allodynia effect of 8-OaS may be related to the suppres-sion of spinal astrocytes via decreasing the phosphorylation of AKT-mTOR signaling pathway resulting in attenuating the development of neuropathic pain.