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TL;DR
Researchers developed a chemogenetic system to silence specific pain-sensing neurons in mice and found that it reversed signs of chronic neuropathic and bone cancer pain without affecting normal touch sensation.
eNeuro · 8 authors, 2 centres
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Researchers developed a chemogenetic system to silence specific pain-sensing neurons in mice and found that it reversed signs of chronic neuropathic and bone cancer pain without affecting normal touch sensation.
This preclinical study tested a novel chemogenetic tool (PSAM4-GlyR) for silencing sensory neurons. In vitro, varenicline application silenced calcium responses in PSAM4-GlyR-expressing dorsal root ganglion neurons. In vivo, systemic varenicline administration to mice with AAV9-mediated DRG expression reduced pain behaviors in inflammatory and chemotherapy-induced cold allodynia models. The key finding emerged from a Cre-dependent mouse line targeting NaV1.8-positive neurons. In these mice, varenicline elevated withdrawal thresholds in acute pain tests without altering innocuous touch. Crucially, varenicline reversed mechanical, thermal, and cold hypersensitivity in chronic constriction injury (neuropathic pain) and partially reversed weight-bearing deficits in cancer-induced bone pain. The system provided reversible neuronal silencing.