Persistent inflammation alters the density and distribution of voltage-activated calcium channels in subpopulations of rat cutaneous DRG neurons

The impact of persistent inflammation on voltage-activated Ca(2+) channels in cutaneous DRG neurons from adult rats was assessed with whole cell patch clamp techniques, sqRT-PCR and Western blot analysis. Inflammation was induced with a subcutaneous injection of complete Freund's adjuvant (CFA). Dil was used to identify DRG neurons innervating the site of inflammation. Three days after CFA injection, high threshold Ca(2+) current (HVA) density was significantly reduced in small and medium, but not large diameter neurons, reflecting a decrease in N-, L-and P/Q-type currents. This decrease in HVA current was associated with an increase in mRNA encoding the alpha 2 delta 1-subunit complex, but no detectable change in N-type subunit (Ca(v)2.2) mRNA. An increase in both alpha 2 delta 1 and Ca(v)2.2 protein was detected in the central nerves arising from L4 and L5 ganglia ipsilateral to the site of inflammation. In current clamp experiments on small and medium diameter cutaneous DRG neurons from naive rats, blocking similar to 40% of HVA current with Cd(2+) (5 mu M), had opposite effects on subpopulations of cutaneous DRG neurons (increasing excitability and action potential duration in some and decreasing excitability in others). The alterations in the density and distribution of voltage-activated Ca(2+) channels in subpopulations of cutaneous DRG neurons that develop following CFA injection should contribute to changes in sensory transmission observed in the presence of inflammation. (C) 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.