As TLR4 is not the only receptor for HMGB1, and the TLR4 signaling is conducted by both MyD88-depended and MyD88-independent pathway, TLR4 and MyD88 were blocked respectively to observe the effect of TLR4-MyD88 pathway on EM-related pain. This evidence concerns the gene HMGB1 and erythema multiforme.