Tetrahydroxystilbene glucoside relieves the chronic inflammatory pain by inhibiting neuronal apoptosis, microglia activation, and GluN2B overexpression in anterior cingulate cortex

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, and 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 injecting complete Freund’s adjuvant 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, THSG suppressed the upregulation of GluN2B-containing N-methyl-D-aspartate receptors and the downregulation of GluN2A-containing N-methyl-D-aspartate receptors caused by chronic inflammation. In addition, THSG increased Bcl-2 and decreased Bax and Caspase-3 expression by protecting neuronal survival. Furthermore, THSG inhibited the phosphorylation of p38 and the increase of nuclear factor κB (NF-κB) and tumor necrosis factor α (TNF-α). Immunohistochemical staining revealed that THSG blocked the activation of microglia and reduced the release of proinflammatory cytokines TNF-α, interleukin 1β (IL-1β), and interleukin 6 (IL-6). In conclusion, this study demonstrated that THSG had a certain effect on alleviating complete Freund’s adjuvant-induced chronic inflammatory pain.