It all started as a slight, barely noticeable tingle a few seconds after I took my first bite into a suicide wing at a local bar. The spiciness was a bit uncomfortable, but it wasn’t nearly as awful as everyone made it out to be. A few seconds passed, and the burning slowly intensified. Okay, maybe it was a bit spicy, but I can handle it; I’ve had worse. I gave it a few more seconds and that is when the burning really started to escalate; my forehead and hands started to sweat, my tongue felt like it was on fire, and tears started to run down my face. I have made a serious mistake, I thought to myself. Why did I think eating a suicide wing was a good idea? Five minutes and a dozen glasses of water later, the pain finally began to subside. But, for some reason I still do not understand, I took another bite into the wing from hell. Except this time, things seemed different. Although the wing was still spicy, it didn’t seem nearly as spicy as the first time. It felt like my tolerance for pain had increased since the first bite. As an aspiring biochemist, I was naturally curious, so I set out to learn what had happened to my spice sensitivity and why.
The first thing I discovered on my figurative journey was that the fiery feeling in my mouth was due to a molecule known as capsaicin. This molecule and other related molecules (commonly referred to as capsaicinoids) are found in the peppers from plants in the genus Capsicum. Capsaicinoids are produced by the peppers in order to aid in the dispersal of seeds. Plants in this genus use birds as a dispersal method for the seeds, as birds will not damage the seeds by ingesting the peppers. In contrast, seed damage and loss of viability commonly occurs during the consumption of the peppers by mammals. Birds are not affected by capsaicin, but mammals are. Thus, the production of capsaicin deters mammals from consuming the peppers, but birds can consume the fruit without adverse effects.
My second discovery was that capsaicin, and capsaicinoids in general, produce their fiery effects by acting as an agonist for the vanilloid receptor subtype 1 (TRPV1) receptors. These receptors are found on sensory neurons and are responsible for the recognition of heat, the regulation of temperature, and the sensation of pain. When the TRPV1 receptors are exposed to high temperatures (above 42⁰C), the cell depolarizes due to the rapid influx of extracellular calcium ions. This rapid influx of ions initiates a signal transduction pathway and elicits many physiological responses, one of which is a painful burning sensation (See figure 1). This sensation is due to the transmission of a signal from the TRPV1 receptors to the nervous system which, among other things, results in neurogenic inflammation, vasodilation, and an increased heart rate. The transmission of this signal is mediated primarily through two neuropeptides: substance P (SP) and calcium gene-related peptides (CGRP). As an agonist, capsaicin interacts with the TRPV1 receptors such that they are activated and the signal transduction pathway ensues. This means that when I took a bite out of the chicken wing, my mouth felt like it was burning when, in reality, the burning sensation was due to the interaction between capsaicin and the TRPV1 receptors. So, that explains the initial displeasure that I felt after the first bite, but what about the reduction in my sensitivity following the second?
Figure 1. Capsaicin binding to the TRPV1 results in the influx of extracellular calcium ions. This influx initiates a signal transduction pathway resulting in the release of the neuropeptides substance P (SP) and calcium gene-related peptides (CGRP). The influx also activates a calcium/calmodulin dependant enzyme.
Although capsaicin initially causes a burning sensation through the release of SP and CGRP, exposure to the molecules over a longer period of time results in the desensitization of the sensory neuron. This desensitization, which lasts well over two hours, leads to a significant decrease in pain. The desensitization of the TRPV1 receptor explains why my first bite of the suicide wing felt blistering hot, but the second wasn’t nearly as painful. Although researchers agree upon the idea that desensitization occurs following long term exposure to capsaicin, the exact mechanism is still debated. There are currently two theories as to how the desensitization occurs, but recent research suggests that a combination of both theories may be correct. The first theory involves the blocking of SP and CGRP. The second theory involves the failure of the cell to repolarize following the influx of calcium ions. Some researchers believe that the continued activation of the TRPV1 receptor by capsaicin causes the inhibition of the voltage-gated channels responsible for the release of SP and CGRP, which decreases our ability to sense pain. Other researchers believe that the continued activation of the TRPV1 prevents the repolarization of the cell through the continued stimulation of a calcium/calmodulin-dependant enzyme. The continued stimulation of this enzyme results in the dephosporylation and deactivation of many different proteins involved in the TRPV1 signal transduction pathway. In either case, the constant stimulation of the TRPV1 receptors by capsaicin causes desensitization. Therefore, capsaicin has proven to be useful as an analgesic! This point leads me to my final discovery.
Capsaicin has been utilized in a variety of different ways, with two major applications being mace (pepper spray) and as an analgesic. It is used in mace as an eye irritant that is very painful but does not pose any serious health effects. Capsaicin is also utilized as an analgesic for the treatment of ailments such as arthritis, sore muscles, sprains, strains, and bruises. It is most commonly used in topical ointments such as Icy Hot. Although capsaicin is mainly used as an external ointment, researchers have demonstrated that it can also be used through direct injection in order to treat chronic nerve pain. Current research is focusing on new and innovative uses!
When I took my first bite of the suicide wing, I would have never imagined that it would be the catalyst to learning about capsaicin, the TRPV1 receptor, and desensitization. I most certainly did not expect to learn that capsaicin is commonly used in pepper spray and as an analgesic! But that is the great thing about life: we may not necessarily set out to learn new things every time we try something new, but with a curious mind and a positive attitude, we are bound to learn something!