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Scorpion toxin may cure chronic pain

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Researchers have discovered a scorpion toxin that targets the ‘wasabi receptor,’ a chemical-sensing protein found in nerve cells that’s responsible for the sinus-jolting sting of wasabi. Because the toxin triggers a pain response, scientists think it can be used as a tool for studying chronic pain and inflammation, and may eventually lead to the development of new kinds of non-opioid pain relievers.

Researchers at UC San Francisco and the University of Queensland have discovered a scorpion toxin that targets the “wasabi receptor,” a chemical-sensing protein found in nerve cells that’s responsible for the sinus-jolting sting of wasabi and the flood of tears associated with chopping onions. Because the toxin triggers a pain response through a previously unknown mechanism, scientists think it can be used as a tool for studying chronic pain and inflammation, and may eventually lead to the development of new kinds of non-opioid pain relievers.

The scientists isolated the toxin, a short protein (or peptide) that they dubbed the “wasabi receptor toxin” (WaTx), from the venom of the Australian Black Rock scorpion. The discovery came as the researchers were conducting a systematic search for compounds in animal venom that could activate, and therefore be used to probe and study, the wasabi receptor — a sensory protein officially named TRPA1 (pronounced “trip A1”) that’s embedded in sensory nerve endings throughout the body. When activated, TRPA1 opens to reveal a channel that allows sodium and calcium ions to flow into the cell, which can induce pain and inflammation.

“Think of TRPA1 as the body’s ‘fire alarm’ for chemical irritants in the environment,” said John Lin King, a doctoral student in UCSF’s Neuroscience Graduate Program and lead author of a study published August 22, 2019 in Cell, which describes the toxin and its surprising mode of action. “When this receptor encounters a potentially harmful compound — specifically, a class of chemicals known as ‘reactive electrophiles,’ which can cause significant damage to cells — it is activated to let you know you’re being exposed to something dangerous that you need to remove yourself from.”

Cigarette smoke and environmental pollutants, for example, are rich in reactive electrophiles which can trigger TRPA1 in the cells that line the surface of the body’s airway, which can induce coughing fits and sustained airway inflammation.


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