APA
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Vasavda, C., Xu, R., Liew, J., Kothari, R., Dhindsa, R., Semenza, E. R., … Snyder, S. (2022). Identification of the NRF2 transcriptional network as a therapeutic target for trigeminal neuropathic pain. Science Advances.
Chicago/Turabian
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Vasavda, C., Risheng Xu, J. Liew, R. Kothari, R. Dhindsa, Evan R. Semenza, B. Paul, et al. “Identification of the NRF2 Transcriptional Network as a Therapeutic Target for Trigeminal Neuropathic Pain.” Science Advances (2022).
MLA
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Vasavda, C., et al. “Identification of the NRF2 Transcriptional Network as a Therapeutic Target for Trigeminal Neuropathic Pain.” Science Advances, 2022.
BibTeX Click to copy
@article{c2022a,
title = {Identification of the NRF2 transcriptional network as a therapeutic target for trigeminal neuropathic pain},
year = {2022},
journal = {Science Advances},
author = {Vasavda, C. and Xu, Risheng and Liew, J. and Kothari, R. and Dhindsa, R. and Semenza, Evan R. and Paul, B. and Green, D. and Sabbagh, Mark F and Shin, J. and Yang, Wuyang and Snowman, A. and Albacarys, Lauren K. and Moghekar, A. and Pardo-Villamizar, Carlos A and Luciano, M. and Huang, Judy and Bettegowda, C. and Kwatra, S. and Dong, Xinzhong and Lim, M. and Snyder, S.}
}
Trigeminal neuralgia, historically dubbed the “suicide disease,” is an exceedingly painful neurologic condition characterized by sudden episodes of intense facial pain. Unfortunately, the only U.S. Food and Drug Administration (FDA)–approved medication for trigeminal neuralgia carries substantial side effects, with many patients requiring surgery. Here, we identify the NRF2 transcriptional network as a potential therapeutic target. We report that cerebrospinal fluid from patients with trigeminal neuralgia accumulates reactive oxygen species, several of which directly activate the pain-transducing channel TRPA1. Similar to our patient cohort, a mouse model of trigeminal neuropathic pain also exhibits notable oxidative stress. We discover that stimulating the NRF2 antioxidant transcriptional network is as analgesic as inhibiting TRPA1, in part by reversing the underlying oxidative stress. Using a transcriptome-guided drug discovery strategy, we identify two NRF2 network modulators as potential treatments. One of these candidates, exemestane, is already FDA-approved and may thus be a promising alternative treatment for trigeminal neuropathic pain.