Although the mouse model of incisional pain is broadly used, the mechanisms underlying plantar incision-induced nociception are not fully understood. This work investigates the role of Na_v1.8 and Na_v1.9 sodium channels in nociceptive sensitization following plantar incision in mice and the signaling pathway modulating these channels. A surgical incision was made in the plantar hind paw of male Swiss mice. Nociceptive thresholds were assessed by von Frey filaments. Gene expression of Na_v1.8, Na_v1.9, TNF-α, and COX-2 was evaluated by Real-Time PCR in dorsal root ganglia (DRG). Knockdown mice for Na_v1.8 and Na_v1.9 were produced by antisense oligodeoxynucleotides intrathecal treatments. Local levels of TNF-α and PGE₂ were immunoenzymatically determined. Incised mice exhibited hypernociception and upregulated expression of Na_v1.8 and Na_v1.9 in DRG. Antisense oligodeoxynucleotides reduced hypernociception and downregulated Na_v1.8 and Na_v1.9. TNF-α and COX-2/PGE₂ were upregulated in DRG and plantar skin. Inhibition of TNF-α and COX-2 reduced hypernociception, but only TNF-α inhibition downregulated Na_v1.8 and Na_v1.9. Antagonizing NF-κB and p38 mitogen-activated protein kinase (MAPK), but not ERK or JNK, reduced both hypernociception and hyperexpression of Na_v1.8 and Na_v1.9. This study proposes the contribution of the TNF-α/p38/NF-κB/Na_v1.8 and Na_v1.9 pathways to the pathophysiology of the mouse model of incisional pain.