First, the team expressed the gene PSAM4-GlyR, a chemogenetic system based on the human protein receptors nicotinic acetylcholine and glycine, in mouse sensory neurons. They activated PSAM4-GlyR with the clinically approved drug varenicline, which inhibited sensory neurons and also reduced the pain hypersensitivity normally associated with arthritis or nerve injury in mice. Then, the researchers went on to activate the PSAM4-GlyR system in sensory neurons derived from a patient with erythromelalgia, a condition characterised by burning pain. The researchers have shown the translational potential of engineering human protein receptors for the treatment of pain. The full paper, 'A humanized chemogenetic system inhibits murine pain-related behavior and hyperactivity in human sensory neurons', can be read in Science Translational Medicine.
