Liu X, Zhou J L, Chung K, Chung J M
Marine Biomedical Institute, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1069, USA.
Brain Res. 2001 May 4;900(1):119-27. doi: 10.1016/s0006-8993(01)02274-0.
In an attempt to identify important ion channels contributing to the generation of ectopic discharges, the present study examined the effects of ion channel blockers on ectopic discharges of injured sensory neurons after spinal nerve ligation. The main focus of the study was to examine the effect of the sodium channel blocker, tetrodotoxin (TTX), in order to identify important subtype(s) (i.e. TTX-sensitive and TTX-resistant) of sodium channels that are involved in ectopic discharge generation. In addition, the effects of potassium and calcium channel blockers were also tested for comparison with the results of previous studies. The 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 placed in an in-vitro recording chamber consisting of multiple compartments that were independently perfused with 35 degrees C artificial cerebrospinal fluid (ACSF). Single unit recordings were made from teased DR fibers. Once a spontaneously active unit was found and characterized, ACSF containing a channel blocker was perfused to the DRG, the site where almost all ectopic discharges originate after spinal nerve ligation. All the recorded spontaneously active units were found to be Abeta and Adelta fibers (no C fibers were detected). Perfusion of the DRG with a sodium channel blocker (lidocaine) at a dose much less than that required to block conduction of action potentials, significantly inhibited ectopic discharges in all recorded fibers. In 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-resistant subtypes of sodium channels. The data suggest that TTX-sensitive sodium channels are likely to be involved in the generation of ectopic discharges. The present study also confirmed the results of previous studies on the additional potential roles of potassium and calcium channels, thus suggesting that multiple ion channels are likely to be involved in the generation of ectopic discharges.
为了确定促成异位放电产生的重要离子通道，本研究检测了离子通道阻滞剂对脊神经结扎后受损感觉神经元异位放电的影响。该研究的主要重点是检测钠通道阻滞剂河豚毒素（TTX）的作用，以确定参与异位放电产生的重要钠通道亚型（即TTX敏感型和TTX耐药型）。此外，还测试了钾通道和钙通道阻滞剂的作用，以便与先前研究的结果进行比较。在大鼠脊神经结扎后7 - 14天，将受损节段的背根神经节（DRG）连同背根（DR）和脊神经一并切除。将组织置于一个体外记录室中，该记录室由多个隔室组成，这些隔室分别用35摄氏度的人工脑脊液（ACSF）灌注。从分离的DR纤维上进行单单位记录。一旦发现并鉴定出一个自发活动单位，就将含有通道阻滞剂的ACSF灌注到DRG，即脊神经结扎后几乎所有异位放电起源的部位。所有记录到的自发活动单位均为Aβ和Aδ纤维（未检测到C纤维）。用远低于阻断动作电位传导所需剂量的钠通道阻滞剂（利多卡因）灌注DRG，可显著抑制所有记录纤维中的异位放电。此外，以远低于阻断TTX耐药型钠通道所需剂量（平均22.1 nM）的TTX灌注DRG，也可抑制异位放电。数据表明，TTX敏感型钠通道可能参与了异位放电的产生。本研究还证实了先前关于钾通道和钙通道其他潜在作用的研究结果，因此表明多种离子通道可能参与了异位放电的产生。
