Hyperexcitability in sensory neurons is known to underlie many of the maladaptive changes associated with neuropathic pain. Chemogenetics has shown promise as a means to suppress such excitability, yet chemogenetic approaches suitable for human translation are needed. PSAM4-GlyR is an ultrapotent humanised modular ion channel, activated by chemically inert compounds, or clinically-approved drugs. This system can reversibly silence both mouse sensory neurons, and human IPSC derived sensory neurons, via chloride mediated shunting inhibition. Taking a gene therapeutic approach, viral expression of PSAM4-GlyR selectively in mouse sensory neurons, produced potent, reversable, and repeated silencing of sensory behaviours, upon agonist administration. We applied it to both inflammatory and neuropathic pain models. Mechanical and spontaneous pain readouts were ameliorated by PSAM4-GlyR activation in a joint pain inflammation model. Furthermore, suppression of mechanical hypersensitivity generated by a spared nerve injury model of neuropathic pain was also observed upon activation of the channel. As a final step we took a clinical model of human nociceptor hyperexcitability, hIPSC derived sensory neurons generated from a patient with inherited erythromelalgia (due to a gain-of-function mutation in Nav1.7). PSAM4-GlyR activation, was able to silence and reduce the spontaneous activity observed in this model.