Chemogenetics is a process where molecules that control the excitation (stimulation) of neurons are engineered so they only become active in the presence of a non-toxic drug. This process has already shown promise as a means of suppressing such excitability in research involving animals. Jimena Perez-Sanchez, a postdoctoral research scientist at the Nuffield Department of Clinical Neurosciences and joint author of the study with Steven Middleton, and her colleagues have now shown that there is a chemogenetic approach that is suitable for human applications.
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.