Doctor Pepper
By Heather Welch, Environmental Science, 2020
What do hot chili peppers, wasabi, and scorpion venom all have in common? They make you go “ouch” — but why? Dr. David Julius, a professor of physiology at the University of California, San Francisco, was awarded the prestigious Breakthrough Prize in Life Sciences this year for his research on this topic.
The decades of research done by Julius and his colleagues led up to their discovery of the importance of transient receptor potentials (TRPs) in the perception of pain and temperature. TRPV1, the TRP involved in the perception of chili peppers, is a protein that sits on the surface of nerve cells. As an ion channel, it remains closed until something activates it. The capsaicin in chili peppers activates TRPV1 and allows ions (sodium and calcium) to enter through the channel. Once the ions have entered, neurons travel through a relay from the periphery — wherever you touched the hot chili pepper — up through the spine and to the brain, where the signal is translated as a painful burning sensation.
Interestingly, TRPV1 is the TRP that is involved in actual heat perception; the reason that it also detects chili peppers is that the vegetable long ago evolved to mimic a heat stimulus in order to fend off predators. TRPV1 is also activated by compounds from other plant and animal species, such as lemons and some spider venoms, and can detect some chemicals that the body produces in response to inflammation.
TRPV1 is the [receptor protein] involved in actual heat perception; the reason that it also detects chili peppers is that the vegetable long ago evolved to mimic a heat stimulus in order to fend off predators.
Julius has studied other related channels — one of them being TRPA1. Julius refers to TRPA1 as the “wasabi” receptor because it is the channel that responds to the compounds in wasabi to trigger that strange sensation when just a little bit too much has been consumed. WaTx, a toxin emitted by the black rock scorpion, was discovered by Julius’s team to be a novel activator of TRPA1 in that it elicited physical behaviors from the ion channel that were distinct to the toxin. This identification may prove to have pharmaceutical and therapeutic value as there is now a known compound that can be used to alter the state of TRPA1 and improve inflammatory responses in patients.
The growing knowledge of pain, as well as the molecules and neurofibers involved in it is exciting; it is easier to develop a treatment approach to pain when its molecular causes are known. Research is currently being done on the potential of TRPV1 and similar molecules such as TRPA1, as analgesic sites, particularly for conditions such as arthritis and other inflammatory diseases. This is due to the inflammatory indicators that the molecules detect and their role in pain hypersensitivity after injury.
The growing knowledge of pain, as well as the molecules and neurofibers involved in it is exciting; it is easier to develop a treatment approach to pain when its molecular causes are known.
Other channels are also being discovered as useful in the treatment of pain. A team of researchers studied the sodium channel Nav1.7, focusing on how to emulate mutations that cause pain indifference in humans. Because of the effect of these mutations, compounds that inhibit the channel would be advantageous as analgesics for treating pain. The researchers identified a peptide extracted from centipede venom, Ssm6a, that “potently and selectively blocks the human Nav1.7 channel.” In rodent models, the peptide was more effective than morphine as an analgesic. The opposite of TRPV1 — TRPM8 — is involved in real cold perception and is triggered by the menthol in mint. Activation of the channel may be used to mechanically produce analgesia in chronic pain sites.
Though exciting research is happening, development in medicine and pharmaceuticals is always slow and faces many obstacles. For instance, the development of treatments involving the chili pepper TRP is slowed down by the fact that in some cases, treatments targeting TRPV1 inhibit patients from sensing noxious heat, which is dangerous to health. Obstacles, of course, are meant to be overcome; perhaps someday soon, arthritis may be safely alleviated by pharmaceutical control of the TRPV1 channel.
DOI: 10.1016/j.toxicon.2012.04.336
DOI: 10.1016/j.cell.2019.07.014
DOI: 10.1073/pnas.1306285110