Figure 4

Figure 4

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).