期刊
JOURNAL OF NEUROSCIENCE
卷 38, 期 2, 页码 474-483出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1816-17.2017
关键词
neuropathic pain; paclitaxel; TRPA1; TRPV1; zinc
资金
- National Institutes of Health [R01RGM101218, R01DK103901]
- Center for the Study of Itch, Department of Anesthesiology, Washington University School of Medicine
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-dependent manner. Extracellularly applied zinc also inhibits the function of TRPV1 expressed in HEK293 cells and mouse DRG neurons, which requires the presence of zinc-permeable TRPA1 to mediate entry of zinc into the cytoplasm. Moreover, TRPA1 is required for zinc-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.
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