Effect of sodium channel blocker (mexiletine) on pathological ectopic firing pattern in a rat chronic constriction nerve injury model.
We studied the efficacy of mexiletine as a sodium channel blocker for neuropathic pain by investigating the effect of mexiletine on the pathological ectopic firing pattern in a chronic constriction nerve injury (CCI) model. The experiment was conducted with 60 male Wistar rats. The CCI model was created by loosely ligating the sciatic nerve. After breeding 7 days, the frequency and pattern of ectopic firing antidromically recorded from the sural nerve and the amplitude of antidromic sensory nerve-evoked potential were analyzed. The CCI rats were given an intravenous injection of normal saline and mexiletine (5 or 15 mg/kg). Mexiletine significantly suppressed spontaneous firing frequency, an on-off firing pattern that consisted of cyclic bursting spikes and ectopic firing generation under the hypoxic condition. Mexiletine did not influence the amplitude of A-delta component in the antidromic sensory nerve-evoked potential. Mexiletine suppressed ectopic firing by blocking activity of the abnormal sodium channel at the nerve-injured site and dorsal root ganglion without blocking nerve conduction. This study suggests that mexiletine is useful for treating neuropathic pain in peripheral neuropathy.
Nakamura
Satoru
S
Department of Orthopedic Surgery, Asahikawa Medical College, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, 078-8510, Japan.
Atsuta
Yuji
Y
D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects; D008297:Male; D008801:Mexiletine / Q000494:pharmacology*; D009431:Neural Conduction / Q000187:drug effects*; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries*; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D018709:Statistics, Nonparametric
D026941:Sodium Channel Blockers; D008801:Mexiletine