Pain management by chemogenetic control of sensory neurons

Abstract

In this study, Perez-Sanchez et al.¹ developed a chemogenetic method aimed at alleviating pain in mouse models while dampening excitability in human sensory neurons. This analgesic effect was attained through the introduction of human α7 nicotinic acetylcholine receptor and glycine receptor pore domain via virus-mediated expression in sensory neurons, forming a chloride channel. The activation of this channel was made possible by specific agonists. This study highlights the potential for treating clinical pain by gene therapy.

Figure 1

The process of suppression of pain in mice and human sensory neurons mediated by PSAM4-GlyR Transfection with PSAM4-GlyR creates a chloride channel that responds to specific agonists such as uPSEM792 and varenicline. Activation of PSAM4-GlyR by these agonists leads to the inhibition of mouse DRG sensory neurons, the reduction of synaptic transmission in dorsal horn neurons within the spinal cord’s pain circuitry, and the relief of acute inflammatory pain, chronic arthritis pain, and neuropathic pain in murine models. Notably, the activation of PSAM4-GlyR significantly curbed hyperexcitability observed in iPSC-derived human DRG neurons (hiPSC) obtained from individuals with inherited erythromelalgia.