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. 2017 Oct 6;7:12775. doi: 10.1038/s41598-017-13054-3

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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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Injection of NAPQI in human skin induces pain and axon-reflex erythema. (A) Magnitude and time course of NAPQI-evoked pain in human volunteers after intracutaneous injection to the volar forearm. Pain was rated on a numerical rating scale (NRS) from 0 to 10. With co-application NAC (10 mM), pain following injection of NAPQI was reduced (n = 7, mean ± SEM). (B) Laser Doppler scanning to measure superficial blood flow reveals increased flow after NAPQI injection in comparison to NAPQI and NAC (p ≤ 0.011). (C) Representative pseudocolor image series of NAPQI ± NAC injections in one volunteer. (D) Pain ratings to noxious heat (47 °C, 10 s) increase following intracutaneous injection of NAPQI, but not when co-applied with NAC. Diagrams show responses before after injection of NAPQI alone (right) or in combination with NAC (left) presented as mean ± SEM and responses of all subjects tested (grey lines; *p = 0.018). (E) Only in some volunteers NAPQI alone (right), but not in combination with NAC (left) also increased responses to noxious cold (0 °C, 10 s; p = 0.069).