Substance P is a tachykinin family neuropeptide that functions as a neurotransmitter and neuromodulator. In the CNS, Substance P is involved in the regulation of mood, anxiety, sleep, saiety, reinforcement, respiratory rhythm and pain processing. In nociception, the neuropeptide is released at local spinal cord synapses. Recent research now shows substance P is potentially involved in endothelial cell differentiation as well as diverse roles in neuroinflammatory response. The endogenous receptor for Substance P is neurokinin 1 receptor (NK1 receptor), which belongs to the tachykinin receptor sub-family of GPCRs.