Changes in Na+ Channel Currents of Rat Dorsal Root Ganglion Neurons Following Axotomy and Axotomy-Induced Autotomy

Abstract

Section of rat sciatic nerve (axotomy) increases the excitability of neurons in the L4–L5 dorsal root ganglia (DRG). These changes are more pronounced in animals that exhibit a self-mutilatory behavior known as autotomy. We used whole cell recording to examine changes in the tetrodotoxin-sensitive (TTX-S) and the tetrodotoxin-resistant (TTX-R) components of sodium channel currents ( I Na) that may contribute to axotomy-induced increases in excitability. Cells were initially divided on the basis of size into “large,” “medium,” and “small” groups. TTX-S I Na predominated in “large” cells, whereas TTX-R I Napredominated in some, but not all “small cells.” “Small” cells were therefore subdivided into “small-slow” cells, which predominately exhibited TTX-R I Na and “small fast” cells that exhibited more TTX-S I Na. In contrast to results obtained in other laboratories, where slightly different experimental procedures were used, we found that axotomy increased TTX-R and/or TTX-S I Na and slowed inactivation. The effects were greatest in “small-slow” cells and least in “large” cells. The changes promoted by axotomy were expressed more clearly in animals that exhibited autotomy. Also, the presence of autotomy correlated with a shift in the properties of I Na in “large” rather than “small-slow,” putative nociceptive cells. These trends parallel previous observations on axotomy-induced increases in excitability, spike height, and spike width that are also greatest in “small” cells and least in “large” cells. In addition, the presence of autotomy correlates with an increase in excitability of “large” rather than “small” cells. Increases in TTX-R and TTX-S I Na thus coincide with axotomy-induced increases in excitability and alterations in spike shape across the whole population of sensory neurons. Injury-induced changes of this type are likely associated with the onset of chronic pain in humans.