Satellite Glial Cells Control Sensory Neuron Excitability via the Release of Fibulin-2

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. 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 and heat sensitivity in mice.