Satellite Glial Cells Bridge Sensory Neuron Crosstalk in Visceral Pain and Cross-Organ Sensitization

Following colonic inflammation, the uninjured bladder afferent neurons are also activated. The mechanisms and pathways underlying this sensory neuron cross-activation (from injured neurons to uninjured neurons) are not fully understood. Colonic and bladder afferent neurons reside in the same spinal segments and are separated by satellite glial cells (SGCs) and extracellular matrix in dorsal root ganglia (DRG). SGCs communicate with sensory neurons in a bidirectional fashion. This review summarizes the differentially regulated genes/proteins in the injured and uninjured DRG neurons and explores the role of SGCs in regulation of sensory neuron crosstalk in visceral cross-organ sensitization. The review also highlights the paracrine pathways in mediating neuron-SGC and SGC-neuron coupling with an emphasis on the neurotrophins and purinergic systems. Finally, I discuss the results from recent RNAseq profiling of SGCs to reveal useful molecular markers for characterization, functional study, and therapeutic targets of SGCs. SIGNIFICANCE STATEMENT: Satellite glial cells (SGCs) are the largest glial subtypes in sensory ganglia and play a critical role in mediating sensory neuron crosstalk, an underlying mechanism in colon-bladder cross-sensitization. Identification of novel and unique molecular markers of SGCs can advance the discovery of therapeutic targets in treatment of chronic pain including visceral pain comorbidity.