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. 2020 Mar 4;10:3970. doi: 10.1038/s41598-020-60990-8

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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MMP-13 prevents paclitaxel-induced PIPN in rodents by neuron-extrinsic mechanism. (a–d) Increased sensitivity to heat (a), cold (b) and touch (c,d) following paclitaxel treatment of rats (a–c) and mice (d) compared with controls and upon injection of paclitaxel + CL-82198, n = 5–6 animals per treatment group and 5 replicates. (e–g) Fields of live imaged tdTomato + DRG neurons and neurite tracing (e) and length quantification (f,g) show decreased length upon treatment with either paclitaxel, paclitaxel (0.3 µM) + CL-82198 (10 µM), or paclitaxel (0.3 µM) + DB04760 (10 µM). Data represent mean and SEM from 3 independent experiments. (h,i) Increased cold response and tactile sensitivity is alleviated upon topical application of CL-82198 to the hind paw of paclitaxel-injected rats (n = 5 animals per treatment group).