Journal of pain research · 2026
An Integrated Multi-Tissue Single-Cell Transcriptomic Analysis Highlights the CCL2-CCR2 Signaling Pathway as a Potential Therapeutic Target in Neuropathic Pain.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Gan Xiaofeng, Wang Kailong, Lu Dongming, Tang Hongliang, Xie Junping, Tan Liangyuan, Pang Jun
Аннотация
BACKGROUND: Neuropathic pain involves complex neuroimmune interactions across the somatosensory nervous system, yet a comprehensive multi-tissue cellular landscape remains lacking.
METHODS: We integrated single-cell RNA sequencing data from the sciatic nerve (SN), dorsal root ganglion (DRG), and spinal cord (SC) of spared nerve injury (SNI) mice. The therapeutic potential of the selective CCR2 antagonist RS504393 was evaluated in vivo.
RESULTS: Macrophages dominated the injured SN (40.5%), exhibiting an inferred transcriptional shift from a resident-like Mrc1+ phenotype toward proinflammatory Ccl2+/Spp1+ subtypes. Injury elevated glycolytic activity in SN macrophages and spinal microglia, but suppressed metabolism in DRG neurons. Cell-cell communication analysis predicted enhanced CCL2-CCR2 signaling from peripheral macrophages to sensory neurons in the Pain group. In vivo, RS504393 administration significantly alleviated mechanical and thermal hypersensitivity, reduced spinal inflammatory infiltration, and suppressed microglial activation.
CONCLUSION: This study provides an integrated multi-tissue single-cell analysis of neuropathic pain and highlights the CCL2-CCR2 signaling pathway as a potential non-opioid therapeutic target at the peripheral neuroimmune interface, with pharmacological evidence suggesting downstream central effects.
METHODS: We integrated single-cell RNA sequencing data from the sciatic nerve (SN), dorsal root ganglion (DRG), and spinal cord (SC) of spared nerve injury (SNI) mice. The therapeutic potential of the selective CCR2 antagonist RS504393 was evaluated in vivo.
RESULTS: Macrophages dominated the injured SN (40.5%), exhibiting an inferred transcriptional shift from a resident-like Mrc1+ phenotype toward proinflammatory Ccl2+/Spp1+ subtypes. Injury elevated glycolytic activity in SN macrophages and spinal microglia, but suppressed metabolism in DRG neurons. Cell-cell communication analysis predicted enhanced CCL2-CCR2 signaling from peripheral macrophages to sensory neurons in the Pain group. In vivo, RS504393 administration significantly alleviated mechanical and thermal hypersensitivity, reduced spinal inflammatory infiltration, and suppressed microglial activation.
CONCLUSION: This study provides an integrated multi-tissue single-cell analysis of neuropathic pain and highlights the CCL2-CCR2 signaling pathway as a potential non-opioid therapeutic target at the peripheral neuroimmune interface, with pharmacological evidence suggesting downstream central effects.