Fig. 10

CCI-induced nerve injury leads to neuropathic pain by diverse molecular mechanisms. The CCI-induced neuropathic pain mouse model, in which ligatures are placed loosely around the right common sciatic nerve at the mid-thigh level, causes nerve injury and leads to the release of endogenous TLR4 agonists (such as pathogen-associated molecular patterns [PAMPs] and damage-associated molecular patterns [DAMPs]) in the spinal cord. These agonists activate spinal cord microglia and astrocytes through TLR4, which can lead to increased neuronal activation of autophagy, resulting in the increased regulation of autophagic proteins (Beclin 1, p62) and ultimately leading to neuropathic pain