衛星グリア細胞はフィブリューリン-2の放出を介して感覚ニューロンの興奮性を制御する

Pain remains a major clinical challenge, with current therapies often limited by low efficacy and adverse effects. While excitability of sensory neurons in the dorsal root ganglia (DRG) is central to pain signaling, accumulating evidence highlights the importance of non-neuronal cells in modulating neuronal activity. Here, we identify satellite glial cells (SGCs) as a source of Fibulin-2, an extracellular matrix glycoprotein with diverse roles in nervous system development and repair. Using SGC primary cultures and mass spectrometry, we demonstrate that Fibulin-2 is secreted by SGCs in part via extracellular vesicles. Electrophysiological functional assays reveal that application of recombinant Fibulin-2 to cultured sensory neurons reduces neuronal excitability by modulating Kv4-mediated currents. In vivo , loss of Fibulin-2 leads to reduced Kv4.2 and Kv4.3 expression and heightened mechanical, heat and cold sensitivity in mice. Our findings uncover a novel SGC-sensory neuron signaling mechanism modulating pain sensitivity, suggesting Fibulin-2 as a potential therapeutic target for pain management.

Fibulin-2 is secreted by cultured SGCsFibulin-2 reduces sensory neuron excitability and firing frequencyFibulin-2 acts by modulating Kv4-mediated potassium currentsLoss of Fibulin-2 heightens mechanical, heat and cold sensitivity in mice.