What are capsaicin and TRPV1? Is spicy a painful sensation?

Introduction of Capsaicin and TRPV1

Recently the temperature is going down again, cold weather to enjoy a spicy hot pot mouth numb and spicy feeling really addictive. Is spicy a taste sensation, or a pain sensation? There have been many different opinions, until the progress of science to explain this mystery. In fact, after human contact with chili peppers, the capsaicin in chili peppers is thus released, then connected to the receptor, and last causing pain. Therefore, spicy is actually a pain sensation. It was found that the receptor that receives capsaicin is called TRPV1.

Structure

TRPV1 is composed of six cross-modular units, which form four bodies to perform the effect. The detailed structure is as follows:

It is a cation channel that can be stimulated by exogenous and endogenous substances through ectopic modulation, including: high temperature (at temperatures above 43 degrees Celsius), low pH, Mg²⁺, Ba²⁺, capsaicin, lipids, animal toxins, etc. This channel is present in the central and peripheral nervous system and is involved in the transmission of nociceptive sensations and the integration of pain information.

The following figure shows the structural changes after binding:

Functions

In animal studies, TRPV1 has been found to be involved in body temperature regulation, and selective antagonists cause an increase in body temperature. In humans, the receptor channels regulate body temperature by informing the brain that it should be cooled. This is why the consumption of foods such as chili pepper induces sweating to lower body temperature.

The most widely discussed is its medical applications. Drugs acting on the receptors can be used to treat pain associated with multiple sclerosis, chemotherapy, amputation, and osteoarthritis. In the central nervous system, the channel is thought to be used to treat symptoms such as anxiety and epilepsy, in addition to neuropathic pain.

Clinical Studies

Cardiovascular

1. Coronary artery disease

In endothelial cells, the activation of TRPV1 induces endothelial cells to produce endothelial-type nitric oxide synthase (eNOS), which synthesizes nitric oxide (NO). Nitric oxide relaxes smooth muscle, dilates blood vessels, and reduces the inflammatory response. Studies have shown that in atherosclerotic animals, the dietary administration of capsaicin reduces atherosclerotic mass and inflammation.

2. Myocardial infarction

In addition, studies have shown that capsaicin-sensitive sensory nerves have cardioprotective effects. The reason for this is that it promotes the release of CGRP (Calcitonin gene related peptide) and SP (Substance P).

In cardiovascular terms, stimulation of the receptor is beneficial in general, however, more detailed mechanisms and effects deserve further investigation.

Pain

After exposure to high or repeated doses of capsaicin, the TRPV1 receptor becomes desensitized, leading to inhibition of receptor function. However, the mechanism is not fully understood by scientists. It is speculated that the analgesic effect may be related to the degeneration of sensory fibers.

Other clinical uses of capsaicin

Other clinical uses, such as:

• Obesity: It has an appetite suppressing effect, plus its own low caloric content, can be used to suppress obesity.
• Diabetes: It has the effect of regulating insulin concentration, which in turn helps control blood sugar in diabetic patients.
• Bronchial and allergic diseases: It can desensitize sensory nerve fibers and reduce allergic hyperreactivity.
• Gastrointestinal disorders: The gastroprotective effect lies in the modulation of sensory neurons. 400 μg three times a day can reduce gastric mucosal damage caused by ethanol and indomethacin. In addition, it can reduce NF-κB activity induced by Helicobacter pylori.
• Urinary tract disorders
• Itching

Although capsaicin has a wide range of uses, its application still requires a doctor’s instruction and proper application in order not to spice oneself up before it becomes effective.

References:

1. Yang, F. and J. Zheng (2017). “Understand spiciness: mechanism of TRPV1 channel activation by capsaicin.” Protein Cell 8(3): 169-177. 🔗
2. Szabados T, Gömöri K, Pálvölgyi L, et al. Capsaicin-Sensitive Sensory Nerves and the TRPV1 Ion Channel in Cardiac Physiology and Pathologies. Int J Mol Sci. 2020;21(12):4472. Published 2020 Jun 23. doi:10.3390/ijms21124472 🔗
3. Fattori V, Hohmann MS, Rossaneis AC, Pinho-Ribeiro FA, Verri WA. Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses. Molecules. 2016;21(7):844. Published 2016 Jun 28. doi:10.3390/molecules21070844 🔗
4. Rosenbaum T, Simon SA. TRPV1 Receptors and Signal Transduction. In: Liedtke WB, Heller S, editors. TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades. Boca Raton (FL): CRC Press/Taylor & Francis; 2007. Chapter 5. 🔗