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. 2016 Jun 10;13:142. doi: 10.1186/s12974-016-0609-4

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© The Author(s). 2016

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Fig. 3 — Chronic PLZ normalizes FAI responses in S1, and mechanical nociceptive thresholds, in EAE at clinical onset. a Balanced-contrast pseudocolored montages of representative S1 hindlimb responses from VEH/PLZ-treated CFA/EAE animals at clinical onset. b Group mean (±S.E.) hindlimb FA response intensities at peak (as %∆F/F). EAE-VEH animals (n = 7) showed significantly intensified responses to hindlimb stimulation, compared to CFA-VEH controls (n = 8), CFA-PLZ (n = 4), and EAE-PLZ (n = 9). CFA-VEH, CFA-PLZ, and EAE-PLZ groups did not significantly differ (one-way ANOVA, p ≤ 0.001, all pairwise post hoc comparisons by Holm-Sidak method). c Group mean (±S.E.) hindlimb FA response areas. EAE-VEH animals (n = 7) exhibited significant expansion of hindlimb responses compared to CFA-VEH controls (n = 8), CFA-PLZ (n = 4), and EAE-PLZ animals (n = 9). CFA-VEH, CFA-PLZ, and EAE-PLZ groups did not significantly differ (one-way ANOVA; p = 0.003, all pairwise post hoc comparisons by Holm-Sidak method). d Grand-average FA signal traces (thick traces; ±S.E. thin traces) of hindlimb responses in CFA-VEH (n = 8), CFA-PLZ (n = 4), EAE-VEH (n = 7), and EAE-PLZ (n = 9). At the right, group mean (±S.E.) decay durations. EAE-VEH animals at clinical onset exhibited significantly prolonged decay durations vs. CFA-VEH, CFA-PLZ, and EAE-PLZ animals. CFA-VEH, CFA-PLZ, and EAE-PLZ groups did not significantly differ (one-way ANOVA; p = 0.012, all pairwise post hoc comparisons by Holm-Sidak method). e Group mean (±S.E.) intensities from the (hindlimb) surround-region (as %∆F/F) during the early inhibitory phase (red arrowheads in a). Inhibitory responses in EAE-PLZ mice (n = 9) were significantly more intense than those in EAE-VEH (n = 7). CFA-VEH (n = 8), CFA-PLZ (n = 4), and EAE-VEH groups did not significantly differ (one-way ANOVA, p = 0.007, all pairwise post hoc comparisons by Holm-Sidak method). f Group mean (±S.E.) response thresholds to punctate mechanical stimulation of the hindpaws (Von Frey hairs) for CFA-VEH (7–12 dpi n = 15), CFA-PLZ (12 dpi n = 5), EAE-VEH (n = 14), and EAE-PLZ (n = 17) mice at clinical onset. EAE-VEH mice exhibited significantly reduced mechanical thresholds compared to CFA-VEH controls. Chronic treatment with PLZ from 7 dpi normalized mechanical thresholds in EAE at onset but did not affect thresholds in CFA mice (Kruskal-Wallis ANOVA on ranks, p = 0.005; post hoc comparisons vs. CFA-VEH by Dunn’s method)