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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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PL–periaqueductal gray (PAG) pathway mediates aggravated formalin pain in rats with chronic pain experience. (A) A diagram showing the experiment time line. The clozapine-N-Oxide (CNO)/aCSF micro-injection and formalin test were performed 42 days after virus injection and cannula implantation surgery. CFA injection was performed 28 days before formalin test. (B) AAV5-CaMKIIα-hM4D(Gi)-mCherry virus expression in PL (red, left), expression of hM4Di in PL projection in PAG (red, right). Scale bars: 200 μm. (C) Compared to the control, inhibiting PL–PAG pathway relieved the aggravated phases II formalin pain in the CFA group (the middle column). Detailed pain scores were shown in every 5 min (the right column). n = 8 in each group. In the middle column: ***p < 0.001, hM4Di+aCSF vs. hM4Di+CNO, one-way ANOVA. In the right column: *p < 0.05, **p < 0.01, ***p < 0.001, hM4Di+aCSF vs. hM4Di+CNO, ANOVA with repeated measures and Bonferroni post hoc test.