Antagonizing TRPA1 receptors reduces the BAM8-22-induced itch in humans

Introduction: In most chronic itch conditions, antihistamines are ineffective, highlighting the necessity to study the mechanisms of non-histaminergic itch to develop new treatments. Polymodal C-fibers, transmitting non-histaminergic itch, can be experimentally activated by BAM8-22, a Mas-related G protein-coupled receptor X1 (MrgprX1) agonist. Moreover, TRPA1 ion channel activation could provoke non-histaminergic itch. This study aimed to explore TRPA1 and MrgprX1 interaction by modulating BAM8-22-induced non-histaminergic itch with the TRPA1 antagonist A-967079. Methods: Four areas on the forearms of 22 healthy subjects were treated as follows: vehicle+BAM8-22, A-967079+BAM8-22, A-967079+BAM8-22 (applied after 5 min), and A-967079+inactivated cowhage spicules. BAM8-22 (2 mg/mL) was applied through inactivated cowhage spicules, while A-967079 (0.5 mg/mL) and vehicle were intradermally injected (0.1 mL). After application, itch was scored for 9 minutes, followed by measurement of superficial blood perfusion and mechanical/thermal sensitivities. Results: Itch evoked by A-967079+BAM8-22 (after 5 min) resulted in a lower ( P <0.05) than vehicle+BAM8-22. In A-967079+BAM8-22 (after 5 min) area, mechanically evoked itch was reduced ( P <0.05). Conclusions: The TRPA1 antagonist A-967079 reduced BAM8-22-induced non-histaminergic itch, confirming that the TRPA1 receptors may be involved in non-histaminergic itch generation and hence may provide new information helping manage non-histaminergic itch.