title: Bursting activity in myelinated sensory neurons plays a key role in pain behavior induced by localized inflammation of the rat sensory ganglion.
abstract: Abnormal spontaneous activity of sensory neurons is observed in many different preclinical pain models, but its basis is not well understood. In this study mechanical and cold hypersensitivity were induced in rats after inflammation of the L5 dorsal root ganglion (DRG), initiated by local application of the immune stimulator zymosan in incomplete Freund's adjuvant. Mechanical hypersensitivity was evident by day 1 and maintained for 2 months. The model also showed reduction of rearing behavior in a novel environment. Microelectrode recordings made in isolated whole DRG on day 3 after inflammation showed a marked increase of spontaneous activity, predominantly with a bursting pattern. The incidence was especially high (44%) in Aαβ cells. Spontaneous activity and subthreshold membrane potential oscillations were completely blocked by tetrodotoxin (500 nM) and by riluzole (10 μM), a blocker of persistent sodium currents. In vivo, local perfusion of the inflamed DRG for the first 7 days with riluzole gave long-lasting, dose-dependent reduction in mechanical pain behaviors. Riluzole perfusion did not affect mechanical sensitivity in normal animals. Unmyelinated C cells had a very low incidence of spontaneous activity and were much less affected by riluzole in vitro. Taken together these results suggest that high-frequency and/or bursting spontaneous activity in Aαβ sensory neurons may play important roles in initiating pain behaviors resulting from inflammatory irritation of the DRG.
authors.affiliation: Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0531, USA.
authors.forename: W
authors.initials: W
authors.lastname: Xie
authors.forename: J A
authors.initials: JA
authors.lastname: Strong
authors.forename: D
authors.initials: D
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Shahrestani
authors.forename: J-M
authors.initials: JM
authors.lastname: Zhang
mesh_terms: D000276:Adjuvants, Immunologic / Q000633:toxicity; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D005620:Freund's Adjuvant / Q000633:toxicity; D017950:Ganglia, Sensory / Q000502:physiology*; D005727:Ganglia, Spinal / Q000502:physiology; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000502:physiology*; D015054:Zymosan / Q000633:toxicity
chemical_list: D000276:Adjuvants, Immunologic; D005620:Freund's Adjuvant; D015054:Zymosan