In neuroscience, Substance P is a neuropeptide: a short-chain polypeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family.

Substance P is an 11-amino acid polypeptide with the sequence: Arg Pro Lys Pro Gln Gln Phe Phe Gly Leu Met. In central nervous system substance P has been associated in the regulation of mood disorders, anxiety, stress, reinforcement, neurogenesis, neurotoxicity, nausea / emesis and pain.

The endogenous receptor for Substance P is neurokinin 1 receptor (NK1-receptor, NK1R). It belongs to the tachykinin receptor sub-family of GPCRs.

Substance P antagonist (SPA) aprepitant is available in the market in the treatment chemotherapy induced of nausea / emesis.

Substance P is involved in the transmission of pain impulses from peripheral receptors to the central nervous system. It has been theorised that it plays a part in fibromyalgia. Capsaicin has been shown to reduce the levels of Substance P probably by reducing the number of C-fibre nerves or causing these nerves to be more tolerant.

Naked Mole Rats lack Substance P and do not feel pain when painful stimuli are administered.