Substance P: A New Era, a New Role

Substance P has been extensively studied and is considered the prototypic neuropeptide of the more than 50 known neuroactive molecules. The understanding of substance P has evolved beyond the original concept as the pain transmitter of the dorsal horn. Animal and genetic research, recent developments of nonpeptide substance P antagonists, and important changes in the understanding of neurotransmission have each contributed to the current understanding of substance P. After 7 decades, the physiologic role of substance P is known as a modulator of nociception, involved in signaling the intensity of noxious or aversive stimuli. Genetic studies in mice and development of substance P antagonists provide more recent results that support the redefinition of the central role of substance P. Evidence suggests that this neuropeptide is an integral part of central nervous system pathways involved in psychologic stress.