Diosgenin alleviates neuropathic pain based on the enhancement of autophagy and promotion of M2 polarization.

Neuropathic pain has serious impacts on the quality of people's life. Diosgenin extracted from yams has shown significant potential in the treatment of nervous system diseases. To investigate the potential mechanism of diosgenin fighting against neuropathic pain, we established a chronic compression injury (CCI) model. The pain-related behaviors were determined by Von Frey, hot plate, and sciatic nerve index test. As a result, diosgenin significantly lowered the pain threshold, improved the sciatic nerve index, and decreased the damage of sciatic nerve structure in CCI model mice. It increased the protein levels of LC3-II and Beclin-1, the number of the lysosomes, decreased the protein level of P62 and the number of the autophagosomes, and therefore activated autophagy. Diosgenin also inhibited the proliferation of microglia cells and the translocation of NF-κB p65, while promoting promoted M2 polarization of microglia cells. Autophagy inhibitor like chloroquine inhibited the M2 polarization of microglia cells, and reversed the therapeutic effect of diosgenin. All in all, diosgenin alleviated neuropathic pain in CCI mice based on the enhancement of autophagy and the promotion of M2 polarization.