Ion channels associated with the ectopic discharges generated after segmental spinal nerve injury in the rat

In an attempt to identify important ion channels contributing to the genera tion of ectopic discharges, the present study examined the effects of ion c hannel blockers on ectopic discharges of injured sensory neurons after spin al nerve ligation. The main focus of the study was to examine the effect of the sodium channel blocker, tetrodotoxin (TTX), in order to identify impor tant subtype(s) (i.e. TTX-sensitive and TTX-resistant) of sodium channels t hat are involved in ectopic discharge generation. In addition, the effects of potassium and calcium channel blockers were also tested for comparison w ith the results of previous studies. Thr dorsal root ganglion (DRG) of the injured segment was removed along with the dorsal root (DR) and the spinal nerve 7-14 days after spinal nerve ligation in the rat. The tissue was plac ed in an in-vitro recording chamber consisting of multiple compartments tha t were independently perfused with 35 degreesC artificial cerebrospinal flu id (ACSF). Single unit recordings were made from teased DR fibers. Once a s pontaneously active unit was found and characterized, ACSF containing a cha nnel blocker was perfused to the DRG, the site where almost all ectopic dis charges originate after spinal nerve ligation. All the recorded spontaneous ly active units were found to be A beta and A delta fibers (no C fibers wer e detected). Perfusion of the DRG with a sodium channel blocker (lidocaine) at a dose much less than that required to block conduction of action poten tials, significantly inhibited ectopic discharges in all recorded fibers. I n addition, ectopic discharges were inhibited by TTX perfused to the DRG at a dose much lower (average of 22.1 nM) than that required to block TTX-res istant subtypes of sodium channels. The data suggest that TTX-sensitive sod ium channels are likely to be involved in the generation of ectopic dischar ges. The present study also confirmed the results of previous studies on th e additional potential roles of potassium and calcium channels, thus sugges ting that multiple ion channels are Likely to be involved in the generation of ectopic discharges. (C) 2001 Elsevier Science B.V. All rights reserved.