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. 2018 Jan 2;9:10. doi: 10.1038/s41467-017-02449-5

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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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Fig. 8 — The Poly(A) SPOT-ON reduces pain sensitization in mice produced by intraplantar NGF or IL-6 administration and after plantar incision. a, b Intraplantar injection with vehicle or scrambled SPOT-ON (0.3–1 μg) did not reduce NGF-induced mechanical hypersensitivity or priming produced by intraplantar injection with PGE₂ (100 ng) at day 9 after surgery. c, d Intraplantar injection with Poly(A) SPOT-ON (1 μg) reduces NGF-induced mechanical hypersensitivity and blocked the development of PGE₂-induced hyperalgesic priming. *P < 0.05, **P < 0.01, significantly different from NGF+vehicle group analyzed by two-way ANOVA followed by Bonferroni post hoc test. e, f Intraplantar injection with vehicle or scrambled SPOT-ON (0.3–1 μg) did not reduce IL-6-induced mechanical hypersensitivity or priming produced by PGE₂. g, h Intraplantar injection with Poly(A) SPOT-ON (1 μg) reduces IL-6-induced mechanical hypersensitivity and blocked the development of PGE₂-induced hyperalgesic priming. *P < 0.05, **P < 0.01, significantly different from IL-6+vehicle group analyzed by two-way ANOVA followed by Bonferroni post hoc test. i, j Following plantar incision, local injection with Poly(A) SPOT-ON (10 μg), but not scrambled SPOT-ON (10 μg), reduces mechanical hypersensitivity, contributed to resolution of pain sensitization, and blocked development of hyperalgesic priming when animals were challenged with PGE₂ at day 15. *P < 0.05, **P < 0.01, significantly different from incision+scramble group analyzed by two-way ANOVA followed by Bonferroni post hoc test. k, l Intraplantar injection of the Poly(A) SPOT-ON, but not scrambled SPOT-ON, significantly reduces the development of paw guarding following surgery as well as PGE₂-induced priming. *P < 0.05, **P < 0.01, significantly different from incision+scramble group analyzed by two-way ANOVA followed by Bonferroni post hoc test. m, n Intraplantar injection of the Poly(A) SPOT-ON, but not scrambled SPOT-ON, significantly reduces the presence of facial grimace following surgery and after priming with PGE₂. *P < 0.05, **P < 0.01, significantly different from incision+scramble group analyzed by two-way ANOVA followed by Bonferroni post hoc test. o Paw incision significantly increases the temperature in the incised paw of mice 24 h after surgery. Under these conditions, local administration of the Poly(A) SPOT-ON, but not scrambled SPOT-ON, significantly decreased the incised paw temperature 24 h after surgery. p Quantification of incised and non-incised paw temperature from scrambled and SPOT-ON groups 24 h after surgery. *P < 0.05, **P < 0.01, significantly different from incision+scramble group analyzed by Student's t test. n = 6 per group. For all graphs showing in the figure, data are plotted as mean ± s.e.m.