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. Author manuscript; available in PMC: 2021 May 24.
Published in final edited form as: Expert Opin Ther Targets. 2020 Sep 11;24(10):997–1008. doi: 10.1080/14728222.2020.1815191

Figure 3.

Figure 3

(a) Tissue injury generates a series of inflammatory agents, including reactive oxygen (ROS), nitrogen (nitric oxide) and carbonylic (4-hydroxy-2-nonenal, 4-HNE) species, bradykinin, prostaglandins, histamine, serotonin, kinins, cytokines, neuropeptides, and neurotrophins and chemokines. Some of these agents, such as ROS, cyclopentenone-prostaglandins (cyclo-PGs), nitric oxide, and 4-HNE, directly gate the channel, whereas other agents indirectly modulate TRPA1 activity, thus promoting intracellular signaling cascades. Activation of both pathways contributes to the generation of acute pain. (b) The injured nerve trunk releases proinflammatory chemokines, which recruit activated macrophages within the lesioned area. Phagocyte-dependent oxidative stress (ROS) activates TRPA1 in Schwann cells, which evokes a calcium (Ca2+)-dependent, NADPH oxidase 1 (NOX1)-mediated amplification of hydrogen peroxide (H2O2) release, which targets nociceptor TRPA1 to signal mechanical allodynia.