Molecular mechanisms and therapeutic implications of satellite glial cell-neuron interactions in dorsal root ganglia during cancer-induced bone pain

Cancer-induced bone pain (CIBP) is a complex and debilitating pain state characterized by persistent background pain and breakthrough pain, reflecting the combined effects of tumor invasion, bone destruction, inflammatory responses, and neural dysfunction. Increasing evidence indicates that the dorsal root ganglion (DRG) is not merely a passive relay station in CIBP, but a key site of peripheral sensitization marked by neuronal hyperexcitability, ion channel remodeling, intracellular signaling activation, and transcriptional reprogramming. Although most direct evidence in CIBP has focused on sensory neurons, satellite glial cells (SGCs) have emerged as potentially important regulators of the ganglionic microenvironment because of their close anatomical and functional association with neuronal somata. In other chronic pain states, SGCs have been implicated in potassium buffering, purinergic signaling, gap junction coupling, glutamatergic regulation, and metabolic or oxidative stress responses, all of which may shape nociceptive processing. However, direct evidence specifically defining SGC-neuron interactions in CIBP remains limited, and many mechanistic interpretations are still extrapolated from non-CIBP pain models. In this review, we summarize direct evidence for DRG alterations in CIBP and discuss major molecular pathways that may underlie SGC-neuron crosstalk, including ATP/P2X7/Pannexin-1 signaling, Kir4.1-mediated potassium homeostasis, connexin 43-dependent coupling, and emerging metabolic and stress-related mechanisms. We further evaluate these pathways according to evidence strength, therapeutic potential, and translational relevance. A more precise understanding of ganglionic neuro-glial interactions may provide a stronger mechanistic basis for targeted analgesic development in CIBP.