Cell: Why is mustard onion hot eye? The mechanism behind it helps develop new painkillers

Many people have the experience of tearing away when cutting onions or eating mustardThis is because there is a special substance, the mustard receptor, in onions, mustard and leeksMustard receptors cause people to feel tingling in their eyes, and the body reacts to this pain with stress, which relieves it through a runny nose, tears, and so on, researchers at the University of California, San Francisco, and the University of Queensland recently extracted a toxin (WaTx) against a "mustard receptor" from the venom of a black rock scorpion in AustraliaResearchers looking at specific mechanisms for scorpion scorpion targeting "mustard receptors" found that the scorpion poison causes pain through previously unknown mechanisms, a finding that has undoubtedly contributed to the development of new painkillersThe study was published in the journal Cell"mustard receptor" is the human safety alarm
mustard receptor is actually a calcium channel protein called TRPA1, it is widely found in people's sensory nerves, is the receiving of external environmental stimuli sensorsWhen the mustard receptor is activated, the calcium channel opens and calcium and sodium ions flow into the cells, causing pain and inflammation"Mustard receptors are the body's 'alarm' against chemical stimuli in the environment, and when mustard receptors encounter potentially harmful compounds, they are activated to alert the body to danger," said John Lin King, a doctoral student in neuroscience at the University of California, San Francisco,"
one of the harmful compounds is the focus of monitoring of mustard receptors, which are known as "reactive electrogenesis reagents"Spicy foods such as smoke, mustard, onions and garlic in cigarettes contain compounds that stimulate mustard receptorsnote, inflammatory factors can also activate mustard receptors, so TRPA1 is considered a potential target for the treatment of chronic pain, itching, and neurogenic inflammatory syndrome"bend overtaking" to reveal the pain-inducing mechanism of scorpion poison
researchers have made many attempts to find the specially effective TRPA1 agonisant and reveal its mechanism of action The likes of menthol and cannabinoids are natural TRPA1 agonists, but these compounds are ineffective and less effective , they set their sights on animal venom Animal venom can cause redness, pain and even death After screening, the researchers found that Australia's black rock scorpion virus (Urodacus manicatus) is rich in TRPA1 activators By purifying and separating scorpion poison, the researchers obtained a peptide called the mustard receptor toxin (WaTx) researchers were pleasantly surprised to find that WaTx activates mustard receptors in a different way than the average TRPA1 agonisor WaTx forces entry into cells bypassing the "standard route" and severely restricts the amount of material that enters the cell In general, small to ions, large to molecular, are either ingested by cells through "inner swallowing" or through protein channels on the cell surface into the cell However, WaTx contains an unusual sequence of amino acids that allows it to penetrate the cell membrane directly and inside the cell Few proteins have this ability team then conducted a series of animal trials that showed that injecting TRPA1 activator mustard oil into the mice's claws caused pain, inflammation and swelling In contrast, the mice injected with WaTx had acute pain and allergic reactions, but no swelling The researchers believe that WaTx is a defense mechanism Although almost every animal, including worms and humans, has a form of TRPA1, the researchers found that WaTx only activates this form in mammals Given that black rock scorpions do not eat mammals, toxins are likely to be primarily used to ward off mammals' predators how far are the new painkillers from us? most of the drugs used to relieve pain today are opioids While opioids can be effective in relieving pain, they are highly addictive and lead to drug dependence the findings could give researchers a better understanding of acute pain and provide new insights into the link between chronic pain and inflammation The findings may even lay the groundwork for the development of new painkillers "The discovery of this toxin provides scientists with a new tool for detecting the molecular mechanisms of pain, especially selectively detecting the processes that cause pain allergies," said Dr David Julius, a professor and chair of the , the University of California, San Francisco For those interested in drug discovery, our findings show the potential of TRPA1 as a new non-opioid analgesic to treat chronic pain "