Anxiolytic effects of polydatin through the blockade of neuroinflammation in a chronic pain mouse model

BACKGROUND: Chronic pain is frequently comorbid with anxiety disorder, thereby complicating its treatment. Polydatin, a component from the root of Polygonum cuspidatum, has shown neuroprotection in the central nervous system. However, its effects on pain and anxiety processing have been rarely investigated. In this study, mice were injected with complete Freund’s adjuvant (CFA) at the hindpaw to induce pain- and anxiety-like behaviors. RESULTS: Treatment with polydatin (25 mg/kg) alleviated the anxiety-like behaviors but not pain perception in these mice. Polydatin treatment reversed the upregulation of N-methyl-D-aspartic acid receptors and GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors in the amygdala of CFA-injected mice. Additionally, this treatment reduced the levels of proinflammatory cytokines, namely, tumor necrosis factor-alpha and interleukin-1β, in the amygdala. Furthermore, activated nuclear factor kappa-B signaling was blocked in the amygdala from CFA-injected mice. By using docking technology, we found potential structural binding between polydatin and IκB kinase beta. CONCLUSION: This study indicates the anxiolytic effects of polydatin by suppressing inflammatory cytokines in the amygdala.