Effect of ginsenoside Rg1 on activity of spinal microglia and expression of p38 mitogen-activated protein kinase/nuclear transcription factor-kappa B in neuropathic pain rats

Abstract

Objective To evaluate the effect of analgesia of ginsenoside Rg1(Rg1) in neuropathic pain(NP) and to investigate the changes in activation of both microglial cells in dorsal horn of spinal cord and p38 mitogen-activated protein kinase(p38MAPK)/NF-κB signaling pathway within microglia. Methods Thirty six rats having been intrathecally catheterized successfully were stochastically divided into 6 groups (6 rats for each group) respectively including sham+natural saline group(group A), chronic constrictive injury(CCI)+natural saline group (group B), CCI+low-dose Rg1 group (group C), CCI+middle-dose Rg1 group(group D), CCI+high-dose Rg1 group(group E) and CCI+minocycline group(group F). Among all groups except group A, the left common sciatic nerve of anesthetized rats was exposed to four silk ligatures(3-0) which were tied loosely proximal to the sciatic nerve's trifurcation. Different medicines were injected intrathecally(i.t.) 1 d before and 1 d, 3 d and 5 d after CCI. Behavioral assessment of anti-nociceptive effects was conducted by thermal withdrawal latency(TWL) method. The content of p38MAPK, phosphorylated p65(p-p65)(member of NF-κB superfamily) and ionized calcium binding adaptor molecule-1(IBA-1) was detected by Western blot method. The level of OX-42, one marker of microglia was examined by immunohistochemistry method. Results ① TWL values of group C, group D and group E were significantly higher than value of group B. The effect was in a dose-dependent manner(P<0.05). ② Compared with group B, over-activation of microglia in group C, group D and group E were markedly suppressed, indicated by deeply inhibited expression of IBA-1 and OX-42, two markers of microglia(P<0.05). ③ Phosphorylation of relevant molecules in p38MAPK signaling pathway in comparison to which in group B such as p38MAPK and NF-κB was attenuated abundantly in group C, group D and group E(P<0.05). Conclusions Activation of p38 MAPK/NF-κB signaling pathway in dorsal horn microglia may be a crucial event in the pathogenesis of NP. It is also suggested that Rg1, a new inhibitor of microglia might be a viable therapeutic strategy for treating NP. Key words: Neuropathic pain; Ginsenoside Rg1; Chronic constrictive injury; p38 mitogen-activated protein kinase/nuclear transcription factor-kappa B