The feeling of pain is not something any of us particularly enjoy, but it serves many important functions such as helping us become immediately aware of situations that may be harmful. There are two extremes to pain sensitivity: complete inability to feel pain, which can lead to premature death, and experiencing pain perpetually, which would make performing activities of daily living difficult. Understanding the mechanisms behind pain is key to being able to treat individuals suffering from such conditions. Nociceptors are receptors found at nerve endings, and they are largely responsible for causing us to feel pain when activated. Thus, identifying therapies that either prevent or are involved in the activation of these receptors is one approach being taken by researchers to treat pain. Most recently, studies have identified a new compound that targets one such receptor, TRPA1, which has been shown to be activated by stimuli like wasabi and mustard oil.
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Researchers have found that the venom from the Australian black rock scorpion contains a toxin (WaTx) that is capable of binding to and activating TRPA1. Interestingly, unlike previously known activators, WaTx was shown to be able to pass through a cell’s membrane without any assistance from transporters or processes like endocytosis. The study also demonstrated the differences in changes to TRPA1 after it is bound to WaTx compared to after it is bound to mustard oil. Upon binding to mustard oil, TRPA1 lets sodium and calcium ions into the cell, which depolarizes it and ultimately causes a pain response. In addition, mustard oil’s particular mechanism of activating TRPA1 actually causes more calcium than sodium to flow into the cell, leading to a type of inflammation called neurogenic inflammation. When WaTx binds to TRPA1, however, there is no excess calcium and, as a result, no inflammation.
The findings of this study have multiple implications. In regards to chronic pain management, the researchers noted that the pain elicited from WaTx is more acute and less chronic due to the lack of inflammation, which suggests that it may be possible to separate these two types of pain for future studies. Furthermore, the discovery of a novel activator of TRPA1 indicates that there is a potential to synthesize drugs to target it in order to treat pain-related health conditions. The drugs that activate TRPA1 and similar receptors could help individuals who are unable to feel pain while the drugs that block activation of these receptors could provide relief for those always experiencing pain. Hopefully, these types of medications will be effective, inexpensive, and accessible to all those who need them in the near future.
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