Changes in Membrane Excitability and Potassium Currents in Sensitized Dorsal Horn Neurons of Mice Pups

Abstract

Rationally, an increased intrinsic excitability of dorsal horn neurons could be a factor contributing to alter the gain of the nociceptive system during central sensitization, however direct evidence is scarce. Here we have examined this hypothesis using current and voltage-clamp recordings from dorsal horn neurons in the spinal cord in vitro preparation obtained from mice pups of either sex. Cords were extracted from carrageenan-pretreated and control animals to allow for comparison. Dorsal horn neurons from treated animals showed significantly larger and faster synaptic responses. Synaptic changes started developing shortly after inflammation (1 h) and developed further after a longer-term inflammation (20 h). However, these neurons showed biphasic changes in membrane excitability with an increase shortly after inflammation and a decrease in the longer term. Concomitant changes were observed in transient (I(A)) and sustained potassium currents (I(DR)). Prolonged superfusion of naive spinal cords with NMDA led to a decreased neuronal excitability and to increased potassium currents. Results suggest that excitability plays a role more complex than expected during the process of central sensitization of dorsal horn neurons and that modulation of potassium currents may contribute to shape the changing states of excitability. The decreased excitability observed after long-term inflammation is interpreted as a homeostatic correction to an abnormal state of synaptic activity.