The single-cell transcriptomic atlas iPain identifies senescence of nociceptors as a therapeutical target for chronic pain treatment
Chronic pain remains a significant medical challenge with complex underlying mechanisms, and an urgent need for new treatments. Our research built and utilized the iPain single-cell atlas to study chronic pain progression in dorsal root and trigeminal ganglia. We discovered that senescence of a small subset of pain-sensing neurons may be a key driver of chronic pain. This mechanism was observed in animal models after nerve injury and in human patients with chronic pain or diabetic neuropathy. Notably, treatment with senolytics, drugs that remove senescent cells, reversed pain symptoms in mice post-injury. These findings highlight the crucial role of cellular senescence in chronic pain development, demonstrate the therapeutic potential of senolytic treatments, and underscore the value of the iPain atlas for future pain research. Overall design: DRG was isolated from mice with or without CCI procedure. Nuclei were extracted from frozen DRG. Pooled nuclei were used for snMultiomic. For smartseq3, NeuN positive nuclei were sorted and analyzed.