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. 2017 Sep 4;7:10406. doi: 10.1038/s41598-017-11120-4

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© The Author(s) 2017

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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MOR KO mice show no morphine-induced hyperalgesia following partial sciatic nerve ligation (pSNL). (A) The experimental design shows the schedule for nociceptive measures (arrows). Following determination of baseline (BL) and neuropathic hypersensitivity (14 days post-pSNL, partial sciatic nerve ligation) on a 5 °C cold plate, WT and MOR KO mice were treated for 7 days with either morphine or saline control solution. On d8, allodynia was measured with the cold plate, von Frey filaments and heat plantar tests. (B) Cold pSNL allodynia and OIH (n = 10–12/group), two-way ANOVA, Newman-Keuls test. Morphine induced OIH in WT mice,*p < 0.05 compared to post-pSNL. (C) Mechanical pSNL allodynia (n = 10–12/group), two-way ANOVA, Newman-Keuls test. pSNL induced mechanical allodynia; WT saline group and WT morphine group, p < 0.001 pSNL vs BL; KO saline group and KO morphine group, p < 0.01 pSNL vs BL. Morphine induced OIH in WT mice, *p < 0.05 compared to post-pSNL. (D) Heat pSNL allodynia (n = 10–12/group), two-way ANOVA. Morphine induced no OIH. pSNL induced cold, mechanical and heat allodynia. Detailed statistical analyses are presented in Supplementary Table S5.