Contents

  1. PHYSIOLOGICAL EFFECT OF CAPSAICIN
    1. Intro
      1. Why are people more and more obsessed with spicy food?
      2. What is capsaicin?
      3. Effect of capsaicin
      4. Disadvantages of capsaicin
      5. Additional
    2. TRP (transient receptor potential) channel family
      1. Mechanisms of TRPV1
        1. TRPV1 as a heat sensitive ion channel
        2. TRPV1 as a capsaicin receptor
        3. Desensitization of TRPV1
        4. Other activating factors of TRPV1
        5. Other factors released after activation of TRPV1
    3. Capsaicin on the sensory neurons
      1. Administrating capsaicin physiological effects
      2. Effect of capsaicin on sensory neurons
      3. Effect of capsaicin on the calcium ion release
      4. Effect of capsaicin on Smooth Muscle
      5. Effect of capsaicin on life span
      6. Effect of capsaicin on chronic pain
    4. References
      1. Articles
      2. Websites
      3. Magazines

PHYSIOLOGICAL EFFECT OF CAPSAICIN

Intro

chemicalstructure.png

Figure 1 'Chemical structure of capsaicin'

Have you heard of ‘mukbang’? It is a new trend that is popular among those who create their own YouTube videos. It means broadcasting yourself eating. This is becoming an increasingly popular trend and lots of people watch this. If you search the word mukbang on YouTube, you may find lots of videos people eating many kinds of food. As you scroll down the video list, you will see a variety of foods that are eaten include ‘artificially made spicy’ ingredients. Furthermore, there were YouTube challenges called ‘fire noodle challenge’, or ‘one chip challenge’, which entail eating spicy food and showing people how they react. Why are the people obsessed with these spicy foods? What kinds of chemicals are used to make the food artificially spicy?

Why are people more and more obsessed with spicy food?

'Spicy’ is not a taste. It is the tongue feeling pain when a compound that makes you feel spicy sensation attaches to the surface of the tongue. To lessen the pain, the brain secretes endorphins, which has analgesic effect. Endorphins not only have painkiller effects, but also make people feel happy. This, in effect, lessens stress so people are obsessed with the so-called 'spicy' feeling!

What is capsaicin?

(Cordell et al., 1993)

Effect of capsaicin

Disadvantages of capsaicin

Additional

As stated, capsaicin is a chemical compound that can be extracted from many kinds of chilli peppers. Capsaicin has many beneficial effects. When a person consumes adequate amount of capsaicin by chilli pepper, he or she can expect weight loss effect, increased metabolism, fatigue recovery, and painkilling effect. But when a person overeat capsaicin, it causes because stomach problems like simple stomach ache, to stomach ulcer or chronic gastritis. It is also bad for skin irritation, so be aware not to eat too much spicy food.

TRP (transient receptor potential) channel family

TRP channels are integrated membrane proteins and they work as cationic ion channels, which increase the intracellular cation levels by receiving the chemical or physical stimuli. This changes the membrane potentials. TRP channels have a characteristic structure, which is 6 transmembrane spanning helices, and both N- and C-terminals are located inside the cell. It is understood that the complete channels are tetramers with a pore formed by them. These channels are present in all types of cells in the body (Tominaga, 2013).

2.png

Figure 2 'TRPV1 receptor'

Mechanisms of TRPV1

TRPV1 as a heat sensitive ion channel

TRPV1 (Transient receptor potential vanilloid member 1 channel) is one of TRP ion channel family, and it is also well known as “Capsaicin receptor”. This receptor is aligand-gated (nonselective, cation) ion channel receptor, but it also has the property of the voltage-gated ion channel as well (Rosenbau & Simon, 2007). However, in this essay we only focus on ligand-gated ion channel property since its voltage-gated property is minor and not clearly identified. It detects the heat (43℃: the threshold that the organisms feel pain) and opens the ion channel, so Ca2+ and Na+ flow into the cell (Rosenbau & Simon, 2007). The mechanism of the heat sensation has not been clarified yet, but some of the TRP ion channel family are considered to be the heat sensors (Tominaga, 2013). However, other TRPV receptors such as TRPV2-6 are not heat sensitive (Samanta et al., 2018). The influx of cations causes the depolarization of the cell and then emission of the action potential. This signal is recognized as pain. Those TRPV1 receptors are mainly located in the nociceptive neurons of peripheral nervous systems but it is ubiquitous (Mucosa of GI tract etc.) (Tominaga, 2013; Rosenbau & Simon, 2007).

TRPV1 as a capsaicin receptor

TRPV1 can also be sensitized by vanilloid groups such as capsaicin etc. Capsaicin is a lipophilic substance, so it can pass through the membrane and attach to the receptor intracellularly in the peripheral terminals of afferent sensory neurons. When capsaicin is attached to the receptor, the receptor can be activated and it allows Ca2+ and Na+ to flow into the cell. (Figure 2) At the same time, in the presence of capsaicin, the threshold of the heat sensitivity (43℃) is lowered to around 30-35℃, which is lower than the body temperature in the most of domestic animals, and therefore it causes the painful and burning sensation. This means that the hotter the food is, the more pain the individual feels when they eat capsaicin-containing food. Other than capsaicin, other factors such as proton (acidic conditions) can also activate the receptor, and cause the pain (Tominaga, 2013; Rosenbau & Simon, 2007).

Desensitization of TRPV1

In the presence of capsaicin, it causes the burning or painful sensation as described above, but the prolonged exposure to capsaicin actually leads to TRPV1 activity to be declined. This is so-called desensitization of the receptors, and it is caused by increased concentration of intracellular calcium ions. Enzymes such as calcineurin play role in this case to dephosephorylate the receptor proteins. This dephosphorylation makes TRPV1 less sensitive and decrease in response to agonists like capsaicin (Smutzer & Devassy, 2016).

Other activating factors of TRPV1

The sensation of pain through this receptor can be enhanced by phosphorylation of the receptor too. GPCR (G-protein-coupled receptor) has a role on this phosphorylation of the receptor. The inflammatory mediators, such as bradykinin, ATP, protease etc. bind to GPCR and this G-protein activation stimulates PLC (phospholipase C) on the intracellular membrane. The activated PLC breaks down PIP2 (phosphatidylinositol-4, 5-bisphosphate) into IP3 (inositol-1,4,5-triphosphate) and DAG (diacylglycerol). This DAG activates PKC (protein kinase C), which phosphorylate TRPV1. It can also be phosphorylated by PKA, which is activated by cAMP. Stimulatory G-protein plays a role when prostaglandin or serotonin binds to it, and AC (adenylate cyclase) synthesizes cAMP (Figure 3) (Tominaga, 2013).

33.png

Figure 3 'Phosphorylation of the receptor'

Other factors released after activation of TRPV1

Activation of TRPV1 induces the secretion of CGRP (Calcitonin gene-related peptide) and substance P (and ATP, which is not well clarified) (Figure 4)(Tominaga, 2013). CGRP is known for its vasodilator effect in the cerebral arteries and therefore induces migraine. However, they also have advantageous physiological effects on the GI tract, such as increasing blood circulation, inducing GI tract activity, and suppressing secretion of gastric juice. Its vasodilator effect can be beneficial in neurovascular protection from vasoconstriction due to cerebral or cardiac ischemia (Grell et al., 2019).

signal.png

Figure 4 'Signal of the sensation'

Capsaicin on the sensory neurons

Capsaicin is a general stimulator of nociceptive sensory neurons which translates signals to the brain and the spinal cord in case of an injury. Capsaicin stimulates afferent sensory neurons primarily by opening a cation channel. This process is mediated directly by a specific membrane receptor. Antagonists of capcasain give rise to the activation of the nociceptive sensory neurons. Subsequently capsaicin exhibits anti inflammatory property and is wildly used in clinical practice (Szolcsányi, 2004).

Administrating capsaicin physiological effects

Effects of capsaicin vary according to the route of administration. The Dorsal Root Ganglion (DRG) neurons are destroyed however the C fibres’ (slow conducting fibres C fibres in the somatic nervous system mediate pain sensation) axons and terminal ends of the neurons undergo morphological changes in the central nervous system. There has been no evidence of the effect of capsaicin on the motor system.

Neurotensin, regulator of Luteinising Hormone (LH) and prolactin found in the central nervous system neurons show no changes or effects. When admistered to newborn rats, capsaicin causes the reduction of substance P, a tachykinin of paracrine effect, in the sensory neurons (Arnold et al, 1980).

The effect of Capsaicin was investigated to determine catecholamine secretion of the adrenal medulla collective hormones. Intravenous administration of capsaicin stimulated the sympathetic activity of the adrenal gland. The higher the dosage of administration was, the higher the stimulus was in the adrenal gland sympathetic activity. It was concluded that capsaicin act mainly through the stimulation of the central nervous system. (Figure 5)

effects.png

Figure 5 'Effects of capsaicin'

Effect of capsaicin on sensory neurons

Capsaicin inhibits the axonal/axoplasmatic transport of sensory neurons. Evidence for this phenomenon, capsaicin was injected to the sciatic nerve blocks. An accumulation of somatostatin and substance P were measured at the site of injection within 24 hours. The long term depletion of substance P is unlikely and shall return back to normal levels within 1 or 2 weeks. The possibility of having capsaicin receptor in the axon rather than the nerve endings may exist. Capsaicin acts on the terminal ends of C fibres in both the central and peripheral nervous system without affecting the sensory neurons. Substances transported to the terminals will influence their recovery accordingly. Capsaicin stimulates or inhibits nociceptive sensory neurons called vanilloid receptor 1. These neurons exhibit inflammatory pain, regulate homeostasis as well as metamorphosis. Capsaicin sensitive neurons are modified by stress leading to a change in the metabolic development (Schultz and Ustinova, 1998).

Radio Immuno Assay (RIA) studies have shown that corticotropin releasing hormone (CRF) was found in the same location with substance P, enkephalin (involved in the nociceptice regulation in the body) and somatostatin in the dorsal horn of the spinal cord. Capsaicin administration resulted in a decline in the concentration of substance P, Vasoactive Intestinal Peptide (VIP), Cholecystokinin (CCK) and CRF whereas somatostatin and enkephalin concentration remained unchanged. It was concluded that primary afferent neurons located specifically in certain regions of the spinal cord were sensitive to the effects of capsaicin injected while topical capsaicin caused a decline of the above mentioned substances only at the terminal end of the sensory neurons (Skofitsch et al, 2003).

Effect of capsaicin on the calcium ion release

Capsaicin increases the intracellular calcium ions levels via ryanodine sensitive calcium ion channel, activated in the sarcoplasmatic reticulum. Phosphotidyl inositol triphosphate, which opens the ligand dependent intracellular calcium ion channels, however does not play a role in this phenomenon (Cholewinski et al, 2003).

Effect of capsaicin on Smooth Muscle

Capsaicin is used in identifying neurotransmitters dealing with afferent neurons through the transient receptor potential vanilloid (TRPV1) at the spinal level. The most important transmitters to stimulate a local efferent response of capsaicin are tachykinins and calcitonin. Effects of these interactions might differ in humans and animals by the mediation of Vasoactive Intestinal Peptide (VIP) and Nitric Oxide (NO) (Barthó et al, 2004).

Effect of capsaicin on life span

In central Asia and African countries, there is a belief that diets rich in spicy food, life expectancies of people are considerably prolonged just by incorporating a variety of spices. Scientific research has demonstrated that low concentration of capsaicin in everyday diet has shown little to no evidence in extending life. However, Capsaicin reduces the daytime activity in females contributing to a longer life (Shen J et al, 2019).

Effect of capsaicin on chronic pain

Changes in the environment surrounding the sensory endings causes hypersensitisation by the activation of TRPV1. During Prolonged pain or inflammatory processes, sensation of pain leads to an over expression of TRPV1 by the A delta and Type c fibres. In the presence of an axonal trauma, axonal transport of nociceptive transmitters contributes to the onset of chronic pain (Russell and Burchiel, 2003).

References

Articles

Cholewinski, A., Burgess, G. M., & Bevan, S. (2003, March 18). The role of calcium in capsaicin-induced desensitization in rat cultured dorsal root ganglion neurons. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/0306452293903157#!

Cronkleton, E. S. and E. (2018, September 2). How Does Cayenne Pepper Help You Lose Weight? Retrieved from https://www.healthline.com/health/food-nutrition/cayenne-pepper-for-weight-loss

Grell, A.-S., Haanes, K. A., Johansson, S. E., Edvinsson, L., & Sams, A. (2019, October 4). Fremanezumab inhibits vasodilatory effects of CGRP and capsaicin in rat cerebral artery - Potential role in conditions of severe vasoconstriction. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/S0014299919306788

Rosenbaum, T., & Simon, S. A. (2007). TRPV1 Receptors and Signal Transduction. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK5260/?report=classic

Russell, L. C., & Burchiel, K. J. (2003, March 10). Neurophysiological effects of capsaicin. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/0165017384900055#!

Saljoughian, M. (2009, July 20). Capsaicin: Risks and Benefits. Retrieved from https://www.uspharmacist.com/article/capsaicin-risks-and-benefits

Schultz, D, H., Ustinova, & E, E. (1998, May 1). Capsaicin receptors mediate free radical-induced activation of cardiac afferent endings. Retrieved from https://academic.oup.com/cardiovascres/article/38/2/348/299436

Shen, J., Shan, J., Zhu, X., Yang, P., Zhang, D., Liang, B., … Dai, Z. (2019, November 29). Sex specific effects of capsaicin on longevity regulation. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/S0531556519305169

Skofitsch, G., Zamir, N., Helke, C. J., Savitt, J. M., & Jacobowitz, D. M. (2003, January 27). Corticotropin releasing factor-like immunoreactivity in sensory ganglia and capsaicin sensitive neurons of the rat central nervous system: Colocalization with other neuropeptides. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/0196978185900579

Smutzer, G., & Devassy, R. K. (2016, January 14). Integrating TRPV1 Receptor Function with Capsaicin Psychophysics. Retrieved from https://www.hindawi.com/journals/aps/2016/1512457/

Suo, S., Ishiura, S., & Tol, H. H. M. V. (2004, August 23). Dopamine receptors in C. elegans. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/S0014299904007307

Szolcsányi, J. (2004, November 24). Forty years in capsaicin research for sensory pharmacology and physiology. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/S0143417904000757

Tominaga, M. (2013). 温度感受性TRPチャネル. Science of Kampo Medicine '漢方医学, 37(3), 164–175. doi: http://tenaca-nips-2016.kenkyuukai.jp/images/sys\information\20161004145432-C9A0307CDC5BFFBE368042C37301506118242A368CDD5986EDA4A983ED7B8D92.pdf

Vlachová, V., Lyfenko, A., Orkand, R. K., & Vyklický, L. (2004, August 5). The effects of capsaicin and acidity on currents generated by noxious heat in cultured neonatal rat dorsal root ganglion neurones. Retrieved from https://physoc.onlinelibrary.wiley.com/doi/full/10.1111/j.1469-7793.2001.t01-1-00717.x

Watanabe, T., Kawada, T., Kurosawa, M., Sato, A., Iwai, K., Ishii, H., … Department of Food Science and Technology. (1988, July 1). Adrenal sympathetic efferent nerve and catecholamine secretion excitation caused by capsaicin in rats. Retrieved from https://journals.physiology.org/doi/abs/10.1152/ajpendo.1988.255.1.E23

Websites

Magazines