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. 2018 May 8;8:7122. doi: 10.1038/s41598-018-25581-8

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© The Author(s) 2018

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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MIA leads to a increased sensitivity of endogenous opioid signaling within the RVM. EMG characterization of the nociceptive withdrawal reflexes in rats. Thresholds for mechanically evoked EMGs were significantly reduced in MIA-treated rats compared to saline rats at 14 (A) and 28 days (B) following intra-articular injection of MIA. Intra-RVM administration of 3 ng DAMGO did not alter MIA induced reductions in EMG threshold at Day 14 (A), but did reverse this reduction at Day 28 in MIA rats (B). Intra-RVM administration of DAMGO (3 ng) significantly inhibited EMG response magnitude to threshold vFh stimulation in saline (white bars) and MIA (black bars) treated rats at Day 14 compared to baseline (pre-drug) values. Low dose DAMGO (3 ng) was reduced EMG responses to threshold stimuli (C) in MIA treated rats at both Day 28 compared to saline treated controls but high dose DAMGO (30 ng) reduced responses at both Day14 and 28. A similar but not identical pattern was seen following DAMGO to responses to suprathreshold stimuli (D). Threshold determinations were compared using a one-way ANOVA with Bonferroni post-test. EMG magnitude and duration were compared between groups using a two-way repeated measures ANOVA with Sidak post-hoc test **p < 0.01, ***p < 0.001, ****p < 0.0001. Day 14: MIA (n = 27 rats); Saline (n = 29 rats). Day 28: MIA (n = 50 rats); Saline (n = 38 rats). All data are presented as mean ± SEM.