Too hot to handle

February 2, 2021

Written by: Lisa Wooldridge

Many are familiar with the experience of biting into a surprisingly spicy dish. Our mouths feel warm, our lips and tongues burn, we start to sweat, and our noses run. Extremely spicy food can leave the entire face throbbing in pain. Why is this experience so dramatic? You can blame capsaicin and your TRPV1 receptors.  

Capsaicin is a chemical found in peppers that is responsible for making them spicy. Capsaicin strongly and specifically binds to a receptor called the TRPV1 ion channel, or the transient receptor potential vanilloid type 1 channel, which is located on the cell membranes of specific neurons. These TRPV1 receptors sense changes in temperature near neurons on the mouth and skin and then convey that information to the brain. Although TRPV1 receptors are found on our tongues and in our mouths, they are not part of the brain’s taste system. Tastes (salty, sweet, bitter, sour, and umami) arise when we eat food containing specific chemicals. These chemicals activate receptors on specialized taste receptor cells that cluster together into taste buds. Flavor is different than taste and arises from a combination of multiple senses including taste, smell (olfaction) and touch (somatosensation). TRPV1 receptors are actually part of the somatosensory nervous system, which is responsible for bodily sensations such as touch and pain. 

Capsaicin causes its burn by altering the way TRPV1 receptors respond to temperatures. Usually, temperatures above 43°C (or 108°F) – the approximate temperature where heat becomes uncomfortable to the touch – cause TRPV1 channels to open¹. When the channel opens, a flood of positive ions rushes into the neuron and makes it more likely to fire. When capsaicin binds to TRPV1, the channel changes shape. The new shape allows temperatures as low as 34°C – a few degrees below normal body temperature – to open the channel¹. Since the channel normally opens in response to very hot temperatures, the brain interprets the channel opening as heat (See figure 1). This is why you experience a sudden sensation of heat, even though the temperature in your mouth hasn’t changed at all!  In fact, there is a similar explanation for why mint leaves your mouth feeling cold. The menthol found in mint interacts with TRPM8, a channel related to TRPV1, that usually responds to cold temperatures².

TRPV1 channels opening explains why spicy foods cause a hot sensation, but what about the other effects of spicy foods? TRPV1 receptors are primarily located on a pain-specialized class of neurons called C-fiber nociceptors¹. Since these neurons are normally activated by painful stimuli, they initiate a host of responses to protect the body from an injury. For example, C-fiber nociceptors release “pro-inflammatory” chemicals that recruit immune cells and trigger an inflammatory response that creates the throbbing and burning pain in our mouths. If the food is spicy enough, capsaicin can even make its way to the TRPV1 receptors in our nasal passages or our eyes, where similar pro-inflammatory responses cause our eyes and noses to run. In addition to alerting the body to its sudden “injury”, the activity of TRPV1 receptors on C-fibers also tells the body to cool down in response to the perceived heat, resulting in sweating¹. These familiar effects are all the body’s way of responding to a threat – just, in this case, one that doesn’t actually exist. 

If capsaicin is able to trick the body into thinking it’s on fire, why is it that some people love spicy food, while others can’t handle any? Although no one knows exactly why, both nature and nurture seem to contribute to a person’s spice preference. Identical twins are more likely than fraternal twins to share spice preference and tolerance³, indicating that genes play a role in spice enjoyment. However, eating spicy food repeatedly can also build tolerance in most people. This tolerance is likely due to a process called desensitization, where cells expressing TRPV1 receptors become less sensitive to the effects of capsaicin after multiple exposures. As a result, it will take more capsaicin to produce the same burning feeling. Scientists aren’t sure why this tolerance occurs, but it may be the result of changes in the shape of the receptor⁴, damage to the cells¹, or removal of the receptor from the neuron’s surface⁵. Finally, other chemicals in capsaicin-containing peppers endow spicy foods with flavors beyond their burn. Some scientists think that activation of TRPV1 receptors indirectly affects taste receptor cells and enhances the perception of these other chemicals, which could make the experience of eating the pepper-rich foods more enjoyable for spice lovers⁶.

The burning pain evoked by capsaicin may make you wonder why it even exists. The most popular theory is that it serves as a defense mechanism for pepper plants. Fruits – including peppers – evolved so that plants could protect and spread their seeds. Mammals who might try and eat peppers would chew right through their relatively delicate seeds, destroying them in the process. The theory is that the unpleasant burn from the capsaicin teaches mammals to leave pepper plants alone. In contrast, birds swallow their food whole and do not destroy pepper seeds during digestion. Conveniently, the TRPV1 receptors of birds are unaffected by capsaicin, allowing them to happily eat peppers and spread the intact seeds⁷. This difference helps another generation of peppers thrive – and allows you to enjoy that spicy ramen for another day.  

References:

1. Szallasi A, Blumberg PM. Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev. 1999;51(2):159-212.
2. Liu B, Fan L, Balakrishna S, Sui A, Morris JB, Jordt SE. TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. Pain. 2013 Oct;154(10):2169-77. doi: 10.1016/j.pain.2013.06.043. 
3. Törnwall O, Silventoinen K, Kaprio J, Tuorila H. Why do some like it hot? Genetic and environmental contributions to the pleasantness of oral pungency. Physiol Behav. 2012;107(3):381-389. doi:10.1016/j.physbeh.2012.09.010
4. Docherty RJ, Yeats JC, Bevan S, Boddeke HW. Inhibition of calcineurin inhibits the desensitization of capsaicin-evoked currents in cultured dorsal root ganglion neurones from adult rats. Pflugers Arch. 1996;431(6):828-837. doi:10.1007/s004240050074
5. Liu J, Du J, Wang Y. CDK5 inhibits the clathrin-dependent internalization of TRPV1 by phosphorylating the clathrin adaptor protein AP2μ2. Sci Signal. 2019;12(585):eaaw2040. Published 2019 Jun 11. doi:10.1126/scisignal.aaw2040
6. Roper SD. TRPs in taste and chemesthesis. Handb Exp Pharmacol. 2014;223:827-871. doi:10.1007/978-3-319-05161-1_5
7. Jordt SE, Julius D. Molecular basis for species-specific sensitivity to “hot” chili peppers. Cell. 2002 Feb 8;108(3):421-30. doi: 10.1016/s0092-8674(02)00637-2. PMID: 11853675.

Cover Photo by Anton Darius on Unsplash