Inflammatory mediators potentiate high affinity GABAA currents in rat dorsal root ganglion neurons

Abstract

Following acute tissue injury action potentials may be initiated in afferent processes terminating in the dorsal horn of the spinal cord that are propagated back out to the periphery, a process referred to as a dorsal root reflex (DRR). The DRR is dependent on the activation of GABAA receptors. The prevailing hypothesis is that DRR is due to a depolarizing shift in the chloride equilibrium potential (ECl) following an injury-induced activation of the Na+–K+–Cl−-cotransporter. Because inflammatory mediators (IM), such as prostaglandin E2 are also released in the spinal cord following tissue injury, as well as evidence that ECl is already depolarized in primary afferents, an alternative hypothesis is that an IM-induced increase in GABAA receptor mediated current (IGABA) could underlie the injury-induced increase in DRR. To test this hypothesis, we explored the impact of IM (prostaglandin E2 (1μM), bradykinin (10μM), and histamine (1μM)) on IGABA in dissociated rat dorsal root ganglion (DRG) neurons with standard whole cell patch clamp techniques. IM potentiated IGABA in a subpopulation of medium to large diameter capsaicin insensitive DRG neurons. This effect was dependent on the concentration of GABA, manifest only at low concentrations (<10μM). THIP evoked current were also potentiated by IM and GABA (1μM) induced tonic currents enhanced by IM were resistant to gabazine (20μM). The present data are consistent with the hypothesis that an acute increase in IGABA contributes to the emergence of injury-induced DRR.