Figures & data
Figure 1. Phylogenetic tree of the eukaryote TRP ion channels superfamily
Figure 2. Structure of the TRPA1 channel. The TRPA1 channel is a homotetramer with each subunit containing six transmembrane helices, a series of ankyrin repeats, and intracellular NH2- and COOH-termini. The transmembrane helices are labeled S1-S6. Orange box reports a list of the main TRPA1 agonists
Table 1. Status summary of TRPA1 antagonists
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
