Reversibly and repeatedly controlling pain sensation through photo-dependent activation and deactivation of TRPA1 channels induced by Photoswitches.

Transient receptor potential ankyrin 1 (TRPA1), recognized as a voltage-dependent ligand-gated nonselective cation channel, is closely linked to pain, neuroinflammation, and respiratory diseases. Therefore, investigating the physiological roles of TRPA1 is crucial for the management of conditions such as migraine, allergic rhinitis, chronic cough, and other related diseases. However, conventional pharmacology molecular tools cannot meet the demand of controlling the transient on-off of TRPA1 ion channel due to the lack of high temporal and spatial resolution. In this study, a series of azobenzene derivatives under the PSTR designation were specifically designed and synthesized. Among these, the compound PSTR1c demonstrates the ability to undergo trans/cis-isomerization upon exposure to blue and ultraviolet light, enabling reversible and stable optical modulation of the TRPA1 channel. This innovative molecular tool surpasses the constraints of traditional methods in terms of time and spatial control, offering a valuable asset for investigating the TRPA1 ion channel.