Substance P (SP) is an undecapeptide present in the CNS and the peripheral nervous system. A compound thought to be involved in the synaptic transmission of pain and other nerve impulses.

Capsaicin induces the release of substance P, one of the principal chemo-mediators of pain impulses from the periphery to the central nervous system (CNS). After repeated application, capsaicin depletes the neuron of substance P and prevents its reaccumulation.