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

Neuropeptide Y (NPY) is a 36 amino acid peptide neurotransmitter, which is widely expressed in the central and peripheral nervous systems of mammals. Neuropeptide Y has an important role in the stimulation of the appetite and is relevant to the pathophysiology of anxiety and depressionNeuropeptide Y is one of the most potent stimulators of feeding. At least five distinct G-protein coupled receptors (Y1, Y2, Y4, Y5, and Y6) mediate the actions of NPY. In rodents, repeated administration of Neuropeptide Y leads to hyperphagia and obesity associated with decreased thermogenesis in brown adipose tissue, hyperinsulinemia, hypercorticosteronaemia, reduced plasma testosterone concentrations, and insulin resistance in skeletal muscle. In the cardiovascular system Neuropeptide Y is found in neurons supplying the vasculature, cardiomyocytes, and endocardium, and is involved in physiological processes including vasoconstriction, cardiac remodeling, and angiogenesis. It is increasingly also implicated in cardiovascular disease pathogenesis, including hypertension, atherosclerosis, ischemia/infarction, arrhythmia, and heart failure. Neuropeptide Y is considered to be an anxiolytic endogenous peptide and its levels can be modulated by stress and it may also play a role in the etiology and pathophysiology of posttraumatic stress disorder.