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. 2017 Apr 5;13:1744806917701743. doi: 10.1177/1744806917701743

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© The Author(s) 2017

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

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Figure 4. — (a–c) Time course showing secondary mechanical hyperalgesia and allodynia induced by lower thigh injection of capsacin in PKG-I^fl/fl mice and SNS-PKG-I^−/− mice. (d) Quantitative summary of response threshold to Von Frey filament applied to hindpaw plantar surface showing that capsaicin-induced secondary mechanical hyperalgesia and allodynia was significantly reduced in SNS-PKG-I^−/− mice as compared to PKG-I^fl/fl mice. (e–h) Bilateral mechanical hyperalgesia and allodynia in a model of chronic muscle pain is reduced upon a specific loss of PKG-I in nociceptors. Intramuscular injection of acidic saline in PKG-I^fl/fl mice produced a dramatic, long-lasting mechanical hyperalgesia and allodynia in ipsilateral (e) and contralateral (g) hindpaws, displaying as a leftward and upward shift of stimulus-response curves over basal curves at 24 h and 3 weeks after second muscle acidic saline injection. Both ipsilateral (f) and contralateral (h) hypersensitivity was almost abolished by the deletion of PKG-I in nociceptors, displaying as very little deviation of stimulus-response curves from basal curves upon muscular acidic saline injection. *indicates statistically significant differences (P < 0.05) between basal and capsaicin treatment in PKG-I^fl/fl mice. ^†indicates statistically significant differences (P < 0.05) between PKG-I^fl/fl mice and SNS-PKG-I^−/− mice upon capsaicin treatment (ANOVA, post hoc Fisher’s test, n = 8–10 mice per genotype).