Substance P Is the Peptide of Pain

Substance P coexists with other neurotransmitters and plays a role in pain and stress. It even plays a role in cardiovascular and digestive system functioning.
Substance P Is the Peptide of Pain

Last update: 27 May, 2021

Many different chemicals circulate throughout your body. Substance P is one of them. It works as a neurotransmitter. Experts suggest that it plays a role in various pain-related processes. In this article, we’ll look at some of the properties of this substance. We’ll also explain what it does and why it’s related to pain. Finally, we’ll uncover a few interesting facts about it.

What’s substance P?

There are different types of neurotransmitters: amino acids, amines, and peptides.

Substance P is a peptide. Glutamate and glycine are amino acids. On the other hand, acetylcholine, dopamine, and serotonin are part of the amine group. Substance P acts as a neuromodulator. Ulf von Euler and John H. Gadoum discovered it in the brain and intestine. As a matter of fact, they discovered it by accident when they were looking for acetylcholine.

We find this substance in the central and peripheral nervous systems. More particularly, in the hypothalamus, the gray matter, and the dorsal cord. It’s also in the salivary glands, bile, and gastrointestinal tract.

 Substance P.

Substance P and pain

Substance P is synthesized by nociceptors. They’re receptors that specialize in the uptake of potentially harmful stimuli that induce pain sensations. When a branch of an axon terminal is activated, it leads to the secretion of substance P.

This happens due to the other branches of the axon in the surrounding area. Substance P also causes vasodilation. Furthermore, it releases histamine, which causes secondary hyperalgesia. In other words, it decreases the pain threshold and increases the response to painful stimuli after any local injury.

Bear, Connors, and Paradiso wrote Neuroscience: Exploring the Brain. They state that, although the neurotransmitter of pain afferents is believed to be glutamate, its neurons also contain substance P. This peptide is found in the storage granules at the axonal terminals. In addition, it can be released through high-frequency bursts of action potentials.

More about substance P

As we mentioned above, this substance acts in the mechanisms associated with pain. However, we haven’t yet mentioned one of the most important discoveries concerning this substance: its connection to migraines. In fact, in recent years, experts have been studying its participation in migraines. They recently discovered certain clues regarding this link.

For example, Millán-Guerrero, Pineda-Lucatero, and Pachecho-Carrasco published an article entitled “Migraine. Review of physiopathogeny and future alternative therapy”. They suggested that to potentially cure migraine, scientists should seek drugs that interact directly with substance P.

A woman in pain.

This substance also participates in other areas. For example, it favors tumor cell proliferation. Researchers from the Institute of Neuroscience of Castilla and León found that the use of antagonistic substances to join the receptors of substance P in tumor cells induces their death. However, they’ve only conducted these studies on rodents.

Its other functions

This substance:

  • Stimulates the contraction of smooth vascular and extravascular muscles.
  • Reinforces salivation.
  • Orchestrates the response of the nervous system when stressful situations occur. These might be situations involving pain or aggression.
  • Lowers blood pressure.
  • Stimulates the duodenum.
  • Operates in the cardiovascular system in the form of hypotensive activity.

Substance P is a unique neurotransmitter. Although experts discovered it 80 years ago, new functions are still being attributed to it. They’re also researching to find solutions to various problems in which this substance may play a role.

This substance is so important that it may be the way to cure both cancer and migraines. Hopefully, experts will keep researching it.

All cited sources were thoroughly reviewed by our team to ensure their quality, reliability, currency, and validity. The bibliography of this article was considered reliable and of academic or scientific accuracy.

  • Bear, M. F. Connors, B. W., PAradiso, M.A. Nuin, X.U., Guillén, X.V & Sol Jaquotor, M.J. (2008). Neurociencias la exploración del cerebro. Wolters Kluwer/Lippicott Williams & Wikins.
  • Milan-Guerrero, R., Pineda-Lucatero, A. G., & Pacheco-Carrasco, M.F. (2003). Migraña. Una revisión de la fisiopatogenia y alternativa terapéutica futura. Gac Méd Méx, 139(4), 377-380.
  • Pichel, A. Comprobada la acción antitumoral de agonistas de Sustancia P. Agencia iberoamericana para la difusión de la ciencia y la tecnología. Recuperado de:

This text is provided for informational purposes only and does not replace consultation with a professional. If in doubt, consult your specialist.