Nerve cells contain a chemical-sensing protein called TRPA1. Scientists discovered that this receptor activates a pain response as a warning mechanism to let us know when we are exposed to a class of chemicals known as ‘reactive electrophiles’. Our bodies are hard-wired to consider these chemicals to be a danger to us.
Reactive electrophiles include chemicals commonly found in hot or spicy foods such as wasabi, mustard, ginger, onions and garlic, hence our body’s sinus-jerking response to wasabi and even the tears triggered by chopping onions. It is for this reason that TRPA1 has swiftly become more widely referred to as the ‘wasabi receptor’.
Researchers from the University of California, San Francisco and the University of Queensland believe that this previously unknown mechanism for generating a pain response can be used as a device to study chronic pain and inflammation, with a view to developing an entirely new approach to pain relief. In their paper, published in the journal, Cell, they say that while searching for a specific chemical compound that could activate TRPA1, they hit upon the idea that animal venom may provide a source.
Eventually, they isolated a toxin, which they dubbed the ‘wasabi receptor toxin‘ (WaTx), in the venom of the Australian Black Rock Scorpion. Among other properties, they found that WaTx has the highly unusual ability to pass through cell membranes.
When activated, TRPA1 opens a channel that allows sodium and calcium ions to flow into the cell, inducing pain and inflammation. It is thought that the receptor has evolved as a way to discourage animals from eating certain plants and WaTx has very likely evolved for the same reason. WaTx serves a purely defensive purpose, only activating the type of TRPA1 found in mammals, which do not form part of the scorpions’ diet.
Lead researcher, John Lin King, said “It was surprising to find a toxin that can pass directly through membranes. This is unusual for peptide toxin.
But it’s also exciting, because if you understand how these peptides get across the membrane, you might be able to use them to carry things – drugs, for example – into the cell that can’t normally get across membranes.”
Another interesting observation was that while WaTx triggered a pain response in the same way as the plant-based irritants, it did not cause inflammation. This indicates that it is possible to decouple the pain response from the inflammation often associated with chronic pain.