The toxin, called the "wasabi receptor toxin," comes from the Australian Black Rock scorpion and evolved out of the need to ward off mammalian predators, said researchers from the University of California, San Francisco and the University of Queensland in Australia.
The scorpion's defensive mechanism particularly targets the cell receptor TRPA1 that plays an important role in pain and inflammation. The researchers believe that their findings provide crucial insights for developing non-opioid pain relievers.
According to the researchers, the wasabi receptor toxin, or WaTx, serves a defensive purpose, which stands in stark contrast to most animal venoms that paralyze or kill predators.
It particularly targets the TRPA1, which gets activated once the toxin enters the cell. Embedded in nerve endings throughout the body, TRPA1 then opens to allow sodium and calcium ions to flow into the cell, causing pain and inflammation.
The researchers described TRPA1 as the body's fire alarm for such chemical irritants in the environment. In particular, a class of chemicals known as reactive electrophiles sends the receptor into a frenzy and causes significant damage to cells. Lin King notes that TRPA1 is activated as a way to tell the body that it is under attack.
Cigarette smoke and environmental pollutants, for example, are rich in reactive electrophiles. They trigger TRPA1 in the cells that line the surface of the body's airway, leading to coughing fits and sustained airway inflammation. Pungent foods such as wasabi, onions, mustard, ginger and garlic can also activate TRPA1 through its chemical compounds. The researchers posited that these compounds evolved for the same reason that WaTx did: to discourage animals from eating them.
In the case of WaTx, the team said that it appears to specifically target mammals. Almost all animals are possessed with some form of TRPA1, but WaTx can only activate the form in mammals. (Related: Ancient natural substance may be the newest treatment for cancer: Scorpion venom found to be effective at identifying brain tumors.)
Upon further study of WaTx, the researchers were surprised by how the toxin activates TRPA1, which they noted was different from how pungent-plant chemical compounds work.
Most compounds gain entry into the cell either by cell ingestion or by passing through one of the protein channels lining the cell's surface. However, WaTx forces its way by avoiding the standard routes that limit what's allowed to go in and out. This is because the toxin contains an unusual sequence of amino acids that allows it to pass right through the cell membrane and into the cell's interior.
Once inside the cell, WaTx binds to a site in TRPA1 called the allosteric nexus – the same site targeted by pungent plant compounds and environmental irritants. But unlike WaTx, these compounds alter the chemistry of the allosteric nexus, which triggers the TRPA1 channel to flutter open and closed. Positively charged sodium and calcium ions are then permitted to enter the cell, causing pain. But the channel tends to let in more calcium, which leads to inflammation.
On the other hand, the TRPA1 channel is propped open as WaTx wedges itself into the allosteric nexus. As a result, both ions can freely and indiscriminately flow into the cell. The overall ion levels will be high enough to trigger a pain response but calcium levels will be insufficient to induce inflammation.
The researchers further tested on mice by injecting either mustard oil, a plant irritant that activates TRPA1, or WaTx into their paws. Mice who had mustard oil had the key hallmarks of chronic pain -- acute pain and hypersensitivity to temperature and touch -- as well as significant swelling. Mice who had WaTx, however, only experienced acute pain and pain hypersensitivities. (Related: Simple lifestyle changes to relieve chronic pain.)
"When triggered by calcium, nerve cells can release pro-inflammatory signals that tell the immune system that something's wrong and needs to be repaired," Lin King explained.
The researchers also noted that it's possible to decouple chronic pain and inflammation, which were previously believed to be experimentally indistinguishable.
With these findings, they believe that healthcare practitioners can have a better understanding of chronic pain. They also hope that their study can contribute to the development of non-opioid pain relievers.
"Our findings underscore the promise of TRPA1 as a target for new classes of non-opioid analgesics to treat chronic pain," said Lin King.
Learn more about alternative treatments for chronic pain at Cures.news.