Fig. 8.

Schematic illustration demonstrates MyD88-dependent signaling pathways of neuropathic pain induced by CCI. Nerve injury produces abundant HMGB1and IL-1β in the DRG and SDH. The binding of HMGB1 and IL-1β to their receptors (TLR2/4 andIL-1R, respectively) activates MyD88 in the DRG and SDH, which phosphorylate NF-κB p65 and ERK. Phosphorylated NF-κB p65 subsequently enter the nucleus to regulate the expression of proinflammation cytokines such as TNF-α. Phosphorylated ERK enter the nucleus to induce transcription factors such as AP-1, which regulates the expression of certain cytokines and activates glial cells. All these signaling events consequently result in central and peripheral sensitizations that produce neuropathic pain