New Compound Alleviates Pain by Regulating Biological Channel

NaV1.7 sodium channels are found in nerve cells called nociceptors that transmit pain signals. The sodium NaV1.7 channel has been actively targeted by drug developers; however, there are currently no effective and safe therapies targeting NaV1.7. Now, researchers at the University of Arizona Health Sciences are closer to developing a safe and effective non-opioid pain reliever after a study showed that a new compound they created reduces the sensation of pain by regulating a biological channel linked to pain.

“Drug discovery for chronic pain is at the forefront of this research, and it’s being amplified by the intersection of the COVID-19 pandemic and the opioid epidemic,” said Rajesh Khanna, PhD, associate director of the UArizona Health Sciences Comprehensive Pain and Addiction Center, professor of pharmacology in the UArizona College of Medicine—Tucson, and member of the BIO5 Institute. “Drug discovery is a very arduous process. Our lab looked at a fundamental mechanism of pain, came up with a way to differentiate it from those before us, and found a compound that has the potential as a new non-opioid treatment for pain.”

Their paper, “Selective targeting of NaV1.7 via inhibition of the CRMP2-Ubc9 interaction reduces pain in rodents,” was published in the journal Science Translational Medicine.

Instead of blocking NaV1.7, the researchers wanted to indirectly regulate it. Using a compound they designed and named 194, the researchers regulated NaV1.7 activation in the laboratory using nerve cells from four different species, including humans. In animal models, 194 was effective in reversing pain in six different pain models in both sexes.

Khanna and the team have been working with the National Institutes of Health’s National Center for Advancing Translational Sciences to optimize the compound.

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