Substance P is an undecapeptide member of the tachykinin neuropeptide family mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. The endogenous receptor for substance P is neurokinin 1 receptor although it also activates neurokinin 2 and neurokinin 3. Substance P is involved in the axon reflex-mediated vasodilatation to local heating and wheal and flare reaction. It has been shown that vasodilatation to substance P is dependent on the NK1 receptor located on the endothelium. In contrast to other neuropeptides studied in human skin, substance P-induced vasodilatation has been found to decline during continuous infusion. Preclinical data support the notion that Substance P is an important element in pain perception. The sensory function of substance P is thought to be related to the transmission of pain information into the central nervous system. Substance P coexists with the excitatory neurotransmitter glutamate in primary afferents that respond to painful stimulation. Substance P and other sensory neuropeptides can be released from the peripheral terminals of sensory nerve fibers in the skin, muscle, and joints. It is proposed that this release is involved in neurogenic inflammation, which is a local inflammatory response to certain types of infection or injury. Substance P appears to have an important role in nausea and vomiting. In 2004, the NK1 antagonist aprepitant (brand name Emend) was approved by the U.S. FDA for the treatment of chemotherapy-induced nausea and vomiting