Quercetin attenuates diabetic neuropathic pain by inhibiting mTOR/p70S6K pathway-mediated changes of synaptic morphology and synaptic protein levels in spinal dorsal horn of db/db mice

Abstract

Numerous studies indicate that the changes of synaptic morphology and synaptic protein levels in spinal dorsal horn neurons contributes to the development and maintenance of neuropathic pain. Quercetin, a bioflavonoid compound, has been shown to have analgesic effect in several pain models. However, the underlying mechanism for quercetin to allieviate pain is unclear. Therefore, in this study, we observed the effect of quercetin on diabetic neuropathic pain in db/db mice and explored the underlying mechanisms. Our results showed that chronic quercetin treatment alleviated thermal hyperalgesia in db/db mice. Moreover, quercetin administration significantly reduced the total dendritic length, the number of dendritic branches, and the dendritic spine density in the spinal dorsal horn neurons of db/db mice. Meanwhile, the up-regulated expressions of synaptic plasticity-associated proteins postsynaptic density protein 95 (PSD-95) and synaptophysin in spinal dorsal horn of db/db mice were decreased by quercetin treatment. In addition, quercetin treatment reduced the phosphorylated levels of mammalian target of rapamycin (mTOR) and p70 ribosomal S6 kinase (p70S6K) in spinal dorsal horn of db/db mice. These results demonstrate that quercetin may alleviate diabetic neuropathic pain by inhibiting mTOR/p70S6K pathway-mediated changes of synaptic morphology and synaptic protein levels in spinal dorsal horn neurons of db/db mice. These findings suggest that quercetin may be a promising therapeutic drug in neuropathic pain.