Satellite glial cells in sensory ganglia: their possible contribution to inflammatory pain.
Neurons in dorsal root ganglia (DRG) are surrounded by an envelope of satellite glial cells (SGCs). Little is known about SGC physiology and their interactions with neurons. In this work, we investigated changes in mouse DRG neurons and SGC following the induction of inflammation in the hind paw by the injection of complete Freund's adjuvant (CFA). The electrophysiological properties of neurons were characterized by intracellular electrodes. Changes in coupling mediated by gap junctions between SGCs were monitored using intracellular injection of the fluorescent dye Lucifer yellow. Pain was assessed with von Frey hairs. We found that two weeks after CFA injection there was a 38% decrease in the threshold for firing an action potential in DRG neurons, consistent with neuronal hyperexcitability. Injection of Lucifer yellow into SGCs revealed that, compared with controls, coupling by gap junctions among SGCs surrounding adjacent neurons increased 2.7-, 3.2-, and 2.5-fold one week, two weeks, and one month, respectively, after CFA injection. In SGCs enveloping neurons that project into the inflamed paw this effect was more enhanced (5.4-fold). Interneuronal coupling was augmented by up to 7% after CFA injection. Pain threshold in the injected paw decreased by 13%, 16%, and 11% compared with controls at one week, two weeks, and one month, respectively, after CFA injection. Intraperitoneal injection of the gap junction blocker carbenoxolone prevented the inflammation-induced decrease in pain threshold. The results show that augmented glial coupling is one of the major events occurring in DRG following inflammation. The elevation in pain threshold after carbenoxolone administration provides indirect support for the idea that augmented intercellular coupling might contribute to chronic pain.
Dublin
Pavel
P
Laboratory of Experimental Surgery, Hebrew University-Hadassah Medical School, Mount Scopus, Jerusalem 91240, Israel.
Hanani
Menachem
M
D000200:Action Potentials / Q000276:immunology; D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D016009:Chi-Square Distribution; D004195:Disease Models, Animal; D005260:Female; D005620:Freund's Adjuvant; D005727:Ganglia, Spinal / Q000166:cytology / Q000276:immunology* / Q000503:physiopathology; D017629:Gap Junctions / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D007249:Inflammation / Q000139:chemically induced / Q000150:complications* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009437:Neuralgia / Q000150:complications* / Q000276:immunology; D009475:Neurons, Afferent / Q000187:drug effects / Q000276:immunology*; D017288:Pain Threshold / Q000502:physiology; D027161:Satellite Cells, Perineuronal / Q000187:drug effects / Q000276:immunology*
D005620:Freund's Adjuvant; D002229:Carbenoxolone