The neuropeptide substance P (SP) is an important member of the tachykinin receptor family , it exert its biological action through transmembrane G-protein coupled receptors. SP and its preferential ligands neurokinin-1 receptor (NK1R) are abundantly expressed in central and peripheral nervous system. Neuropeptides, including Tachykinins are molecular messengers that regulate multiple functions in the central and periphery nervons systems via G-protein-coupled receptors. Two naturally occurring NK1R a ' classic' fulllength receptor (NK1R-FL) and a truncated (NK1R-Tr) mediate the effects of SP. The human NK1R gene is divided into five exons, allowing the generation of multiple splice variants. The only splice variant identified in human tissues at mRNA and protein level is the isoform which lacks 96 amino acid residues at the C-terminus.SP exerts different effect by coupling NK1R-FL and NK1R-Tr on central and peripheral nervous system.