Zinc inhibits TRPV1 to alleviate chemotherapy-induced neuropathic pain

Jialie Luo, Alexis Bavencoffe, Pu Yang, Jing Feng, Shijin Yin, Aihua Qian, Weihua Yu, Shenbin Liu, Xuan Gong, Tao Cai, Edgar T. Walters, Carmen W. Dessauer, Hongzhen Hu

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11 Scopus citations

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.

Original languageEnglish
Pages (from-to)474-483
Number of pages10
JournalJournal of Neuroscience
Volume38
Issue number2
DOIs
StatePublished - Jan 10 2018

Keywords

  • Neuropathic pain
  • Paclitaxel
  • TRPA1
  • TRPV1
  • Zinc

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    Luo, J., Bavencoffe, A., Yang, P., Feng, J., Yin, S., Qian, A., Yu, W., Liu, S., Gong, X., Cai, T., Walters, E. T., Dessauer, C. W., & Hu, H. (2018). Zinc inhibits TRPV1 to alleviate chemotherapy-induced neuropathic pain. Journal of Neuroscience, 38(2), 474-483. https://doi.org/10.1523/JNEUROSCI.1816-17.2017