In the present study, we showed that overproduction of SP significantly increases the severity of sepsis in a TRPV1-dependent manner; and that this phenomenon occurred under the influences of the proinflammatory effects of H2S. Additionally, we found that the underlying signal transduction pathway by which H2S, SP and TRPV1 interact to instigate neural inflammatory processes involve activation of the ERK-NF-κB pathway. This evidence concerns the gene NFKB1 and Sepsis.