Inhibition of hyperpolarization-activated current by ZD7288 suppresses ectopic discharges of injured dorsal root ganglion neurons in a rat model of neuropathic pain

Peripheral nerve injury causes ectopic discharges of different firing patterns, which may play an important role in the development of neuropathic pain. The molecular mechanisms underlying the generation of ectopic discharges are still unclear. In the present study, by using in vivo teased fiber recording technique we examined the effect of ZD7288, a specific blocker of hyperpolarization-activated current (I-h), on the ectopic discharges in the dorsal root ganglion (DRG) neurons injured by spinal nerve ligation. We found that ectopic discharges of all three firing patterns (tonic, bursting and irregular) were dose- and time-dependently inhibited by local application of ZD7288. Interestingly, the extent of suppression was negatively related to frequency of firing prior to application of ZD7288. We also observed that ZD7288 could alter the firing patterns of the ectopic discharges. At 100 muM, tonic firing pattern was gradually transformed into bursting type whereas at 1 mM, it could be transformed to integer multiples firing. These results indicate that I-h might play a role in the generation of various forms of ectopic discharges in the injured DRG neurons and may thus be a possible target for neuropathic pain treatment. (C) 2004 Elsevier B.V. All rights reserved.