Sodium aescinate ameliorates chronic neuropathic pain in mice via suppressing JNK/p-38-mediated microglia activation

Abstract

Abstract A study confirmed that sodium aescinate (SA), a traditional Chinese medicine extracted from the dried ripe fruits of the aescin plant chestnut, can effectively relieve bone cancer pain, but its role in neuropathic pain (NP) remains confused. This study aimed to investigate whether SA has a protective effect on NP and its underlying mechanisms. Thirty mice were randomly divided into three groups (n = 10 per group): sham + vehicle, chronic contraction injury (CCI) + vehicle, CCI + SA. SA (40 µg/L, intrathecal injection) was administered once daily for 5 consecutive days starting on day 7 after surgery. The mechanical withdrawal thresholds (paw withdraw threshold, PWT) of the contralateral and ipsilateral paws of mice in each group were subsequently detected daily. The results displayed that repeated SA treatment could prominently increase the reduction of PWT induced by CCI in the ipsilateral paw of mice. Downregulation of p- c-Jun N-terminal kinase (JNK) and p-p38 protein levels and reduction of microglial activation marker Iba-1-positive ratio, M1/M2 ratio of microglia, and proinflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, in the spinal cords of CCI-mice was observed after intrathecal SA. The above data illustrated that SA might suppress the activation of microglia and neuroinflammation by selectively inhibiting the JNK/p38 signaling pathway, which in turn alleviated CCI-induced NP in mice.