Effects Of Curcumin On TAK1 And Astrocyte In The Dorsal Horn Of Spinal Cord Of Rats Following Neuropathic Pain

Objectives:To investigate the variation regularity of TAK1 in a rat modal of chronic constriction injury (CCI). To investigate the effects of curcumin on the behavior and the expression of TAK1 and the actiavion of astrocyte in spinal cord dorsal horn in chronic constrictive injury (CCI)rats.Methods:Male SD rats were divided randomly into 7 groups. In group CCI, we established a rat modal of chronic constriction injury on the left sciatic nerve according to Bennett and Xie. In group sham rats only underwent surgery of exposing the left sciatic nerve without ligation. The rest of male SD rats, fitted with intrathecal (i.t.) catheters, were divided randomly into 5 groups:group sham+normal saline,group sham+ DMSO,group sham+curcumin 500μg,group CCI+DMSO/NS,group CCI+curcumin 100μg,group CCI+curcumin 500μg. High purity ((?)98.5%) curcumin (dissolved in 50% DMSO) or 50% DMSO 10μl was intrathecally injected beginning from day 3 to day 6 after surgery. On postoperative day 7,14, rats were sacrified after pain threshold measurement for immunohistochemisty of TAK1 and double immunofluorescent staining for TAK1 and GFAP.Results:1,Compared to group sham, the pain threshold in group CCI significantly decreased at all postoperative timepoints, beginning on day reaching a nadir on day 7 and still existing on day 14. Intrathecal curcumin 100μg (0.33-0.4mg/kg),500μg (1.7-2mg/kg) can both obviously improve the pain-sensitive phenomenon in CCI rats from postoperative day 5(2 days after injection) and reached a nadir on day 7 (4 days after injection) dose dependently. The analgesic effect of curcumin 100μg can last to day 11 while curcumin 500μg can last to day 14.2,Immunonohistochemistry displayed that both TAK1 positive cells expressed mainly in the grey matter, abundantly in all layers, especially densely inⅠ-Ⅱlayers of the grey matter. In group CCI, TAK1 immuno-positive cells in superficial laminae obviously increased from day 3 after surgery, the most on day 7 and lasted to day 14. Curcumin can dose dependently inhibit the TAK1 and GFAP on day 7 and day 14.Conclusions:1. The expression of TAK1 was increased in CCI rats. The increse of TAK1 may play asignificant role in the pathgenesis of neuropathic pain in rat induced by chronic constriction injury to the sciatic nerve.2.Intrathecal curcumin treatment significantly attenuated CCI induced hyperalgesia and inhibited the activation of astrocyte.Curcumin could inhibit the expression of TAK1 and the activation of astrocyte in spinal dorsal horn after periphery nerve injury.