Inflammation-induced increase in evoked calcium transients in subpopulations of rat dorsal root ganglion neurons.

The concentration of intracellular Ca(2+) (Ca(2+)) influences neuronal properties ranging from excitability to neurotransmitter release. Persistent inflammation is associated with changes in the properties of primary afferent neurons ranging from excitability to transmitter release. The purpose of the present study was to determine whether previously described inflammation-induced changes in excitability and transmitter release are associated with changes in the regulation of Ca(2+). Acutely dissociated dorsal root ganglion (DRG) neurons harvested from adult rats 3 days following a hind-paw injection of complete Freund's adjuvant (CFA) or naïve controls, were stimulated with 30 mM K(+) (High K(+)). High K(+) evoked changes in Ca(2+) were assessed with fura-2 ratiometric microfluorimetry. Subpopulations of DRG neurons were defined by cell body diameter, isolectin B4 (IB4) binding, capsaicin (CAP) sensitivity and target of innervation (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbo-cyanine perchlorate labeling). Inflammation was associated with significant increases in resting Ca(2+) and increases in the magnitude and decreases in the decay, of the evoked increase in Ca(2+). The changes in evoked transients were larger in neurons innervating the site of inflammation. Furthermore, there were differences among subpopulations of DRG neurons with respect to changes in magnitude and/or decay of the evoked transient such that the increase in magnitude was larger in small- and medium-diameter neurons than in large diameter neurons while the decrease in the decay was greater in CAP responsive, IB4 positive, small- and medium-diameter neurons than in CAP unresponsive, IB4 negative and/or large-diameter neurons. These changes in the regulation of Ca(2+) were not due to inflammation-induced changes in passive or active electrophysiological properties. Importantly, an inflammation-induced increase in evoked Ca(2+) transients in putative nociceptive afferents may contribute to the pain and hyperalgesia associated with persistent inflammation via facilitation of transmitter release from these afferents.