Satellite Glial Cells of the Dorsal Root Ganglia in Pain: Review of Mechanisms, Functions, and Potential Therapeutic Targets

Satellite glial cells (SGCs) are specialized glial cells found in peripheral ganglia, including the dorsal root ganglia (DRG), where they tightly envelop sensory neuronal somata. Through this intimate bidirectional communication, SGCs actively regulate neuronal homeostasis and excitability and contribute to pain. This review discusses the physiological functions of SGCs in the DRG and the mechanisms underlying their contribution to pain across different conditions, as well as their neuroimmune and reparative roles and their potential as therapeutic targets. The literature reviewed indicates that SGCs contribute to neuronal homeostasis through structural and metabolic support and regulation of neuronal excitability. However, these functions can become altered under pathological conditions, involving changes in gap junction communication, purinergic and glutamatergic signaling, and inflammatory mediator production that are associated with SGC activation, neuronal sensitization and pain initiation and persistence. These alterations have been described across inflammatory, neuropathic, diabetic, chemotherapy-induced, and cancer-associated pain. Recent transcriptomic studies further indicate substantial SGC heterogeneity, suggesting distinct cellular states and functions and highlighting the importance of associated markers for their characterization. Beyond pain, SGCs participate in neuroimmune interactions, immune-related responses, and neuronal repair within the DRG microenvironment. Experimental interventions targeting SGC-associated pathways, including nutraceuticals, have produced analgesic effects in several preclinical models. Overall, SGCs are multifunctional components of the DRG, spanning physiological neuronal support and homeostasis to pathological pain and neuroimmune responses. Further investigation of SGC heterogeneity, functional states, and associated pathways may clarify their contribution to pain and support the development of SGC-associated therapeutic strategies for pain management.