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What is Substance P?

By Helga George
Updated Mar 03, 2024
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Substance P is a small peptide that transmits pain signals from the sensory nerves to the central nervous system. It has also been associated with the regulation of stress and anxiety. This compound is thought to contribute to such painful disorders as arthritis and fibromyalgia.

Peptides are small chains of amino acids. A neuropeptide is a one that is involved in mediating sensations and emotional responses, such as pleasure, pain, thirst, and hunger. Examples are compounds called endorphins, which mediate sensations of pleasure, and substance P, which transmits feelings of pain and anxiety. Such chemicals are known as neurotransmitters, and are the means of communication between nerve cells.

Substance P, also known as SP, is found in the spinal cord and brain. For SP to transmit its signal, it must bind to a molecule that will relay the signal to the central nervous system. Such a compound is known as a receptor. SP binds to a receptor that is part of a family of receptors known as the neurokinin 1 receptors. Thus, the feeling of pain or inflammation in the skin, joints, or muscles is transmitted to the brain to be perceived as pain.

Capsaicin, the compound that gives chili peppers their spicy bite, blocks the activity of substance P. It is used as a topical cream to help relieve the pain of arthritis and other painful conditions. Compounds that inhibit the SP receptor are being examined as potential drugs to relieve pain.

More recently, the role of substance P has been expanded to include responding to noxious stimuli. It appears to integrate pain, anxiety, and stress. As expected with such a role, SP is found in parts of the brain that are known to be involved with emotional behavior. The neurokinin 1 receptors are also found in these regions of the brain.

SP also is also involved with the response to nausea. The center in the brain stem responsible for vomiting contains high levels of SP and an SP receptor. A drug that blocks SP is available commercially to prevent nausea in chemotherapy patients.

It has been theorized that SP may be involved in the development of fibromyalgia, a condition of persistent pain. It is thought that increased levels of SP in the spinal cord might cause a heightened awareness of pain. Thus, a fairly normal stimulus would be perceived by the body as being painful.

SP is part of a family of neuropeptides, including a closely related family member known as neurokinin A, that is produced from the same gene, but is processed differently. Another family member is neurokinin B. There are also differing types of receptors, specialized for the different neurokinins. All bind SP to some degree, however. The biochemistry of substance P is clearly quite complex.

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Discussion Comments
By anon996863 — On Oct 18, 2016

If antinausea meds block sp then do they help block pain? If not why not?

By anon993717 — On Dec 08, 2015

I am a 57year old premenopausal women who has been losing my hair and has what I describe as sore scalp, similar to taking my hair out of a ponytail. I used to have very thick, healthy hair. In fact, up until recently, I have, although I can't put the exact time of losing my hair, it has become very thin around the frame of my face and brittle!

On the advice of someone I have been taking Quercetin and cayenne capsules. I am terrified of losing all my hair. I have a lot of stress in my life and I do not handle stress well. What do you suggest? -- Terri Y.

By Instion — On Dec 09, 2013
I didn't know that Substance P has to do with emotional pain and stress. Very interesting! Would stress relievers such as walking, kickboxing or meditation therefore block this substance's activity?

Are there topical remedies other than creams featuring capsaicin that block SP activity?

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