Substance P

Where it comes from

Made in

The pain-sensing C fibres of the sensory nerves, neurons of the gut wall and brainstem, and some immune cells

Sent out by

Painful, hot or chemical stimulation of nerve endings; it leaves both ends of a sensory neuron, so it acts in the skin and in the spinal cord

Acts on

• Spinal cord (dorsal horn)
• Blood vessels and mast cells
• The vomiting centre (area postrema)
• Gut smooth muscle

What it does

• Passes pain signals into the spinal cord ¹
• Causes the redness and swelling of neurogenic inflammation
• Triggers nausea and vomiting

In medicine

• Aprepitant and its relatives block the NK1 receptor to prevent the nausea of chemotherapy ²
• NK1 blockers failed as antidepressants and as painkillers in trials: aprepitant beat placebo in one early study and then missed in five further trials in major depression ³
• Capsaicin cream works partly by emptying nerve endings of substance P ⁴

Beyond the body’s own use

• High-concentration capsaicin patches for nerve pain work by exhausting the substance P nerve endings in the skin for weeks at a time; pooled trials find a modest benefit over a control patch in post-herpetic and HIV-related nerve pain ⁴
• Relatives of aprepitant have been tested for chronic itch and chronic cough: serlopitant missed in two phase 3 itch trials, and orvepitant missed its main mark in cough after a positive pilot study
• Nothing containing substance P is approved, and it is not one of the peptides people obtain outside medicine: it is a signal to block or to measure. The open question is why blocking the receptor prevents vomiting and did nothing for pain or mood ³