@article{b9d132d90d624dc6a2fbc3cbd57e3bc8,
title = "Zinc inhibits TRPV1 to alleviate chemotherapy-induced neuropathic pain",
abstract = "Zinc is a transition metal that has a long history of use as an anti-inflammatory agent. It also soothes pain sensations in a number of animal models. However, the effects and mechanisms of zinc on chemotherapy-induced peripheral neuropathy remain unknown. Here we show that locally injected zinc markedly reduces neuropathic pain in male and female mice induced by paclitaxel, a chemotherapy drug, in a TRPV1-dependentmanner.Extracellularly applied zinc also inhibits the function ofTRPV1expressed inHEK293cellsandmouseDRGneurons, which requires thepresenceofzinc-permeableTRPA1tomediateentry of zinc into thecytoplasm.Moreover,TRPA1isrequiredforzinc-induced inhibition of TRPV1-mediated acute nociception. Unexpectedly, zinc transporters, but not TRPA1, are required for zinc-induced inhibition of TRPV1-dependent chronic neuropathic pain produced by paclitaxel. Together, our study demonstrates a novel mechanism underlying the analgesic effect of zinc on paclitaxel-induced neuropathic pain that relies on the function of TRPV1.",
keywords = "Neuropathic pain, Paclitaxel, TRPA1, TRPV1, Zinc",
author = "Jialie Luo and Alexis Bavencoffe and Pu Yang and Jing Feng and Shijin Yin and Aihua Qian and Weihua Yu and Shenbin Liu and Xuan Gong and Tao Cai and Walters, {Edgar T.} and Dessauer, {Carmen W.} and Hongzhen Hu",
note = "Funding Information: Received June 29, 2017; revised Oct. 24, 2017; accepted Nov. 16, 2017. Author contributions: E.T.W., C.W.D., and H.H. designed research; J.L., A.B., P.Y., J.F., and H.H. performed research; J.L., S.Y., A.Q., W.Y., S.L., X.G., T.C., and H.H. analyzed data; J.L. and H.H. wrote the paper. This work was supported in part by National Institutes of Health Grants R01RGM101218 and R01DK103901 to H.H., and Center for the Study of Itch, Department of Anesthesiology, Washington University School of Medicine to H.H. We thank Gina Story (Washington University, St. Louis) for providing the TRPA1 KO mice. The authors declare no competing financial interests. Correspondence should be addressed to Dr. Hongzhen Hu, Center for the Study of Itch, Department of Anesthesiology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8054, St. Louis, MO 63110-1093. E-mail: huh@anest.wustl.edu. DOI:10.1523/JNEUROSCI.1816-17.2017 Copyright {\textcopyright} 2018 the authors 0270-6474/18/380474-10$15.00/0 Publisher Copyright: {\textcopyright} 2018 the authors.",
year = "2018",
month = jan,
day = "10",
doi = "10.1523/JNEUROSCI.1816-17.2017",
language = "English",
volume = "38",
pages = "474--483",
journal = "Journal of Neuroscience",
issn = "0270-6474",
number = "2",
}