{EXPRESS] Tetrahydroxystilbene Glucoside (THSG) relieve the chronic inflammatory pain by inhibiting neuronal apoptosis, microglia activation and GluN2B overexpression in ACC.

Tetrahydroxystilbene Glucoside (THSG) is one of the active ingredients of Polygonum multiflorum. It has been shown to exert a variety of pharmacological effects, including antioxidant, anti-aging, anti-atherosclerosis. Because of its prominent anti-inflammatory effect, we explored whether THSG had analgesic effect. In this study, we used a model of chronic inflammatory pain caused by injection of complete Freund's adjuvant (CFA) into the hind paw of mice. We found THSG, relieved swelling and pain in the hind paw of mice on a dose-dependent manner. In the anterior cingulate cortex (ACC), THSG suppressed the up-regulation of GluN2B-containing N-methyl-Daspartate (NMDA) receptors and the down-regulation of GluN2A-containing N-methyl-Daspartate (NMDA) receptors caused by chronic inflammation. Additionally, THSG increased Bcl-2, and deceased Bax and Caspase-3 expression by protecting neuronal survival. Furthermore, THSG inhibited the phosphorylation of p38 and the increase of NF-κB and TNF-α. Immunohistochemical staining revealed that THSG blocked the activation of microglia and reduced the release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6. In conclusion, this study demonstrated that THSG had a certain effect on alleviating CFA-induced chronic inflammatory pain.