Anyone who has ever unknowingly bitten into a red hot chili pepper remembers the unhappy result – burning, painful sensations that make one’s mouth feel as though it has caught on fire. That painful burning associated with the consumption of a chili pepper comes from compounds known as capsaicinoids, the most well-known of which is capsaicin. (Fun Fact: Capsaicinoids are derived from the compound vanillin, which gives vanilla its delicious taste and smell.) Surprisingly, their “hotness” or “spiciness” is not a taste but rather a sensation. There are no taste buds associated with capsaicinoids. Capsaicin, the active ingredient in chili peppers, is most often experienced as an irritant. Yet the very chemical that causes that pain, capsaicin, has also become a popular pain-reliever found in over-the-counter and prescription medications.
This irony about the calming effects of hot chili peppers is old news for capsaicin pros like Tibor Rohacs, an associate professor in the Department of Pharmacology and Physiology at Rutgers New Jersey Medical School. His work has focused on an ion channel known as TRPV1, the capsaicin receptor, and Piezo2, a newly identified ion channel that mediates touch sensation.
Researchers found capsaicin completely silenced the Piezo2 channels that are activated by mechanical stimuli. This may be an important part of how capsaicin inhibits mechanical pain which is the general term that refers to any type of back pain caused by placing abnormal stress and strain on muscles of the vertebral column. Typically, mechanical pain results from bad habits, such as poor posture, poorly-designed seating, and incorrect bending and lifting motions.
“TRPV1 is a great sensor, at least physiologically, and it has a chemical activator, capsaicin, which we all know is in chili peppers,” Rohacs explained. “They feel hot because they activate a heat-sensitive ion channel and they trick you into the sensation of heat. And it’s also pretty painful. The idea is basically that this pain-causing, heat sensor ion channel does something to the nerve that in the long run, sort of silences them or desensitizes them.” But the effect isn’t just local, the brain also responds by releasing another type of neurotransmitter known as endorphins. Endorphins are the body’s natural way of relieving pain by blocking the nerve’s ability to transmit pain signals. Additionally, the neurotransmitter dopamine, responsible for a sense of reward and pleasure, is also released. In essence, for some people eating large amounts of spicy food triggers a sense of euphoria similar to a “runner’s high”.
Even more promising is the discovery of a capsaicin analog. A cactus-like plant in Morocco is so hot on the Scoville heat index, its active ingredient clocks in at 16 billion units. That’s 10,000 times hotter than the Carolina Reaper, the world’s hottest pepper and 45,000 times hotter than the hottest of Habaneros, and 4.5 million times hotter than a piddling little Jalapeno. Euphorbia resinifera, aka the resin spurge, is not to be eaten. But while that toxicity will lay up any mammal dumb enough to chew on the resin spurge, resiniferatoxin has also emerged as a promising painkiller. Inject RTX, as it’s known, into an aching joint, and it’ll actually destroy the nerve endings that signal pain. Which means medicine could soon get a new tool to help free us from opioids’ grasp.
The human body is loaded with different kinds of sensory neurons. Some respond to light touch, others signal joint position, yet others respond only to stimuli like tissue injury and burns. RTX doesn’t arbitrarily destroy the endings of all these neurons, instead, it binds to a major molecule in specifically pain-sensing nerve endings, called TRPV1 (pronounced TRIP-vee one).
RTX is between 500 and 1,000 times more potent then capsaicin. RTX specifically binds to TRPV1 which resides on a specific class of fibers that only transmits pain. This leaves all the other sensory neurons unaffected. When RTX binds to TRPV1, it props open the nerve cell’s ion channel, letting a whole lot of calcium in. That’s toxic, leading to the inactivation of the pain-sensing nerve endings. This leaves all the other sensory neurons unaffected. Think about it- only the pain is selectively stopped. Not light touch or the ability to walk, only the pain! RTX’s promise lies in this specificity. Opioids target receptors all over the body, not a specific kind of sensory neuron. That’s why there are so many other, unintentional side effects like constipation, sedation respiratory depression, and fuzziness. That, and you have to take opioids constantly, but not so with RTX. Once given, it should last for an extended period of time because it is destroying the fibers without the associated high or addiction potential.
RTX has been tested in pet dogs that suffer from debilitating pain, and the studies have shown promising results. Unlike rodents, dogs experience pain much the way people do. “And they have personalities,” says Andrew Mannes, chief of the department of perioperative medicine at the National Institutes of Health. “We can get insight into their psyches that we can’t with rats.” The NIH is now running a trial of RTX in people with advanced cancer. Although Mannes and his colleagues cannot predict how soon they will have data, pain experts are watching the trial with interest. David Maine, director of the Center for Interventional Pain Medicine at Mercy Medical Center in Baltimore, says there are other ways to kill pain fibers, such as using alcohol to destroy nerves, but they sometimes cause the pain to come roaring back, far worse than before. With RTX you can target where it acts and avoid potential consequences. That would be an incredible advancement in pain management.
Whether you eat them, apply them or some day inject them, capsaicin may be offer incredible pain relief options.