The “Wasabi” Receptor: Gateway to New Pain Medications?

Recently, David Julius, PhD and his group at the University of California San Francisco have created a three-dimensional rendering of TRPA1 receptor, known colloquially as the “wasabi” receptor. The receptor gets its name from the horseradish-like plant commonly found in Japanese food because isothiocyanates, a compound found in wasabi, stimulates the TRPA1 receptors in mouth and tongue nerve cells, resulting in a cascade of events that ultimately signal the brain that the body is experiencing pain. Other pungent chemical irritants that do not necessarily include isothiocyanates, including those released when cutting an onion, eating hot chili peppers, and being around tear gas or air pollution, also activate this cascade.

Now, a fair question at this point would be, “Why should I care about a receptor that responds to compounds found in wasabi and tear gas? I hate Japanese food and being tear gassed.” Well, back in 2006, when Julius initially discovered the receptor, fellow scientists had the same question. Early research showed that the receptor was not only important for detecting outer threats, but was also activated by interior pain signals, such as in cases of tissue damage and inflammation. Due to the receptor’s multifaceted roles, Julius believes that “knowing more about how TRPA1 works is important for understanding basic pain mechanisms.”

The hope for TRPA1 receptor research is that it will become an important target for pain perception intervention. In support of this venture, Julius’s latest work has been to create a three-dimensional model of the TRPA1 receptor with potential drug binding sites mapped on it. The project was a collaborative effort with Yifan Cheng, PhD, a biochemist at UCSF who specializes in single particle electron cryomicroscopy; together, Julius and Cheng were able to create a model showing how the receptor sends distress signals to the brain following contact with certain chemicals. The model includes the binding site for isothiocyanates (the wasabi compound), as well as the binding site of a new experimental drug (see graphic below). Julius is hopeful that the structure “gives pharmaceutical firms…a map for either tweaking the drugs that they have or for developing drugs that might have different properties.”

The demand from both pain researchers and pharmaceutical companies for drugs that work through the TRPA1 receptor is great. It is believed that unlike the current options of analgesics, TRPA1 receptor drugs will directly affect pain perception nerves and ultimately reduce the risk of side effects like addiction (e.g. Oxycodone, Vicodin) or stomach problems (e.g. Acetaminophen/Tylenol). This is important, considering the amount of funding currently going towards pain research: in 2014, the NIH allotted almost nine hundred million dollars towards pain and chronic pain research; similarly, pharmaceutical companies that specialize in pain medications are multi-million dollar industries. Economically and clinically, there are great repercussions that may follow the development of TRPA1 receptor drugs. It will be interesting to see where Julius and his colleagues go from here.

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