Analysis of the Inhibitory Effect of Dihydroartemisinin on Inflammatory Responses in Mice with Neuropathic Pain Induced by the Japanese Encephalitis Virus NS1

Objectives: To elucidate the underlying mechanism through which Dihydroartemisinin (DHA) exerts its influence on mice with Neuropathic Pain (NP) induced by the NS1 protein of the Japanese Encephalitis Virus (JEV). Materials and Methods: 15 C57BL/6N mice were allocated into a control group (normal mice), a model group (NP model induced by NS1), and a DHA group (NP model induced by NS1 and treated with DHA by gavage). Following corresponding intervention treatments for each group, behavioral tests were carried out, and the levels of inflammatory factors and stress injury markers in the brain tissue were detected. Histopathological damage in the brain tissue was visualized using Hematoxylin-Eosin (HE) staining, and the fluorescence intensities of transmembrane protein 119 (TMEM119) and chemokine (C-C motif) ligand 3 (CCL3) were determined. Finally, the expression of the ALK5/SMAD3 pathway in the mouse brain tissue was examined. Results: Under DHA intervention, the struggling time in the Tail-Suspension Test (TST) and Forced-Swimming Test (FST), as well as escape latency, were notably shortened in the DHA group compared to the model group, while the staying time in the Open-Field Test (OFT) was prolonged (p<0.05). Additionally, both the levels of inflammatory cytokines and the degree of stress-induced injury in the DHA group were significantly lower than those in the control group (p<0.05). HE staining results indicated an improvement in the histopathological damage of the brain tissue in the DHA group, accompanied by a decrease in the fluorescence intensities of TMEM119 and CCL3. Furthermore, it was discovered that DHA activated the expression of the ALK5/SMAD3 signaling pathway. Conclusion: DHA alleviates NP in mice by inhibiting the neuro-inflammatory response, which is achieved through the activation of the ALK5/Smad3 signaling pathway.