Dihydromyricetin attenuates neuropathic pain via enhancing the transition from M1 to M2 phenotype polarization by potentially elevating ALDH2 activity in vitro and vivo

Treatment for neuropathic pain as a refractory disease remains unsatisfactory and represents a significant clinical challenge. A highly effective drug is thus urgently needed for neuropathic pain treatment. Dihydromyricetin (DMY) is a flavonoid with a wide range of biological activities. The

Our data demonstrated that DMY alleviated neuropathic pain via enhancing the polarization transition from the M1 to M2 phenotype by potentially elevating ALDH2 activity in vitro and vivo. DMY- or ALDA-1-microglia may have alleviative effects on neuropathic pain. The findings herein provide a promising avenue for neuropathic pain treatment, suggesting a new target, ALDH2, in the treatment of neuropathic pain.

The effect of DMY was investigated in BV-2 cells and lipopolysaccharide (LPS)-induced BV-2 cells. A neuropathic pain model was established via spared nerve injury (SNI) surgery in mice, and the protein expression level was detected via Western blot assay. The percent of M1 and M2 phenotype polarization cells were detected via flow cytometry assay. Immunochemical staining assay was also performed to measure the marker levels of the M1 and M2 phenotype polarization cells and aldehyde dehydrogenase 2 (ALDH2) level, and mechanical pain sensitivity was evaluated via measurement of the mechanical withdrawal threshold.

We found that DMY promoted the transition from M1 to M2 polarization and upregulated the ALDH2 level in vitro and vitro. ALDA-1, an ALDH2 agonist, promoted the switching from M1 to M2 polarization in vivo and vitro. DMY alleviated pain hypersensitivity induced by SNI via enhancing M2 phenotype polarization by elevating ALDH2 activity in mice. After DMY- or ALDA-1-microglia were injected into SNI-induced pain hypersensitive mice, the mechanical withdrawal threshold was increased significantly when compared with the SNI group. Conclusions: Our data demonstrated that DMY alleviated neuropathic pain via enhancing the polarization transition from the M1 to M2 phenotype by potentially elevating ALDH2 activity in vitro and vivo. DMY- or ALDA-1-microglia may have alleviative effects on neuropathic pain. The findings herein provide a promising avenue for neuropathic pain treatment, suggesting a new target, ALDH2, in the treatment of neuropathic pain.