Substance P
An 11 amino acid neuropeptide involved in pain signalling, inflammation, and mood regulation. Substance P acts through the neurokinin-1 (NK1) receptor and is released from sensory nerve endings in response to tissue injury. It is relevant to pain pathways modulated by peptide-based analgesic research.
Technical Context
Substance P (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) belongs to the tachykinin family and acts primarily through the neurokinin-1 (NK1) receptor, a Gαq-coupled GPCR. It is released from small-diameter sensory neurons (C-fibres) in the dorsal horn and from peripheral nerve endings, transmitting nociceptive and pruritic signals. Substance P also mediates neurogenic inflammation by promoting vasodilation, plasma extravasation, and immune cell recruitment. Its role in pain pathways is relevant to understanding the endogenous context in which peripherally restricted analgesics like difelikefalin operate. NK1 receptor antagonists (aprepitant) are approved as antiemetics, demonstrating the therapeutic potential of targeting tachykinin signalling.