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. 2018 Mar 22;11:85. doi: 10.3389/fnmol.2018.00085

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Copyright © 2018 Fan, Fu, Liu, Cui, Yi and Wan.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Inhibiting the phosphorylation of p38 reverses aggravated formalin pain in rats with chronic pain experience. (A) A diagram showing the experiment time line. SB203580/aCSF micro-injection and formalin test were performed 28 d after CFA/saline injection. The cannula implantation surgery was performed 2 weeks before behavior tests. (B,C) SB203580 micro-injection into PL inhibited the hyperphosphorylation of p38 in rats with chronic pain experience, without (B) or with formalin injection (C). Representative Western blots of p-p38, p38 and β-tubulin were shown above the corresponding histogram. n = 6 in each group. ***p < 0.001, CFA+aCSF vs. CFA+SB203580. **p < 0.01, CFA+aCSF+Formalin vs. CFA+SB203580+Formalin, t test. (D) SB203580 micro-injection into PL inhibited the hyperphosphorylation of cAMP-response element binding protein (CREB) after formalin injection in rats with chronic pain experience. Representative Western blots of p-CREB, CREB and β-tubulin were shown above the corresponding histogram. n = 6 in each group. *p < 0.05, CFA+aCSF+Formalin vs. CFA+SB203580+Formalin, t test. (E) Inhibiting the phosphorylation of p38 in PL by SB203580 reversed the aggravated phases II formalin pain in the CFA group, but not the saline group (the middle column). Detailed pain scores shown in every 5 min (the right column). n = 6 in each group. In the middle column: ***p < 0.001, Saline + aCSF/CFA+SB203580 vs. CFA+aCSF, one-way ANOVA. In the right column: *p < 0.05, ***p < 0.001, CFA+aCSF vs. CFA+SB203580, ANOVA with repeated measures and Bonferroni post hoc test.