Therapeutic Effects and Probably Mechanisms of TAK-242 on Diabetic Peripheral Neuropathic Pain in Rats
LU Yi
YAO Jia-yin
YAO Xin-hua
QING Zhao-hui
TONG Hui
LIU Ling
Abstract：Objective To investigate the therapeutic effect and possible mechanisms of HMGB 1-TLR4 axis in the pathogenesis of diabetic peripheral neuropathy ( DPN) .Methods 60 SD rats were randomly divided into the normal control group (NC group), DPN model group (DPN group), and TAK-242 treatment group (TAK group).Behavioral analysis and stimulation experiments were performed on rats , including thermal radiation stimulation , cold plate test and tactile hypersensitivity test .Western blot analysis was used to determine changes of cytokine expression levels in HMGB 1-TLR4 axis including HMGB1, TLR4, MAPK, NF-Кβ, IL-6.Correlations between cytokine expressions and pain be-havior were analyzed .The therapeutic effect of TAK -242 on DPN rat model was observed .Results Thermal radiation , cold stimulation and mechanical tactile ectopic pain threshold in the DPN group were lower than that of the NC group ( P<0.05).HMGB1, TLR4, NF-Кβand IL-6 expression levels in the DPN group were higher than those in the NC group detected by westernblot analysis (P<0.05).TLR4, NF-Кβand IL-6 expression levels in the TAK group was de-creased compared with the DPN group (P<0.05).Conclusion TLR4 inhibitor TAK-242 has a therapeutic effect on DPN animal model by blocking HMGB1-TLR4 axis.
Keywords：TLR4TAK-242HMGB1-TLR4diabetic peripheral neuropathy
Publication Date：2016-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：4( 640-643 )