Augmentation in gap junction-mediated cell coupling in dorsal root ganglia following sciatic nerve neuritis in the mouse

Abstract

Recent findings highlight the participation of central glial cells in chronic pain, but less is known of a comparable role for satellite glial cells (SGCs), in dorsal root ganglia (DRG). Our previous work showed that sciatic nerve axotomy augmented SGC coupling by gap junctions. The aim of the present research was to find out whether similar changes occur in a mouse inflammation model. Sciatic nerve neuritis was induced by complete Freund's adjuvant (CFA), and isolated ganglia were examined 1 week later. Cell coupling was monitored by intracellular injection of the fluorescent dye Lucifer Yellow. Changes in gap junctions were assessed quantitatively by electron microscopy. Withdrawal threshold in the foot on the side of the inflamed nerve decreased from an average of 3.9 g in control to 0.94 g using Von Frey hairs (P<0.05). In CFA-treated animals dye coupling incidence between SGCs belonging to different glial envelopes increased from 6.9% in controls to 22.5% (P<0.05). Whereas in controls there was no coupling between neurons or between neurons and SGCs, after CFA application the incidence of neuron-neuron and neuron-SGC coupling was 8%. Electron microscopy showed formation of bridges between SGC sheaths surrounding different neurons, which were completely absent in controls. The mean number of gap junctions/100 μm2 of surface of the section occupied by SGCs increased from 0.215 in controls to 0.709 (P<0.01) in CFA-treated mice. The size of individual gap junctions remained the same. This is the first evidence for ultrastructural changes in SGCs following inflammation. The results support the idea that SGCs are sensitive to a variety of peripheral nerve injuries. We propose that the observed changes may alter signal transmission in DRG and thus may contribute to chronic pain.