Effect of mexiletine on spontaneous sensory afferent activity in spontaneous diabetic rats (WBN/Kob rats)

Abstract

In this study, we investigated the hypothesis that mexiletine has an inhibitory action on spontaneous sensory afferent activity caused by small fiber neuropathy in diabetic rats (WBN/Kob rats). Gastric administrations of mexiletine (10 mg in 0.3 ml saline) and the local anesthetic agent lidocaine (10 mg in 0.3 ml saline) were made in urethane-anesthetized rats. In 6 of 7 WBN/Kob rats (57-62 weeks of age), spontaneous afferent activity was observed and was significantly inhibited after administration of mexiletine, whereas it was not seen in either WBN/Kob rats (54 weeks of age) or Wistar SLC rats (31 and 35 weeks of age). This inhibitory action of mexiletine was sustained for more than 2 h after the administration. In contrast, lidocaine administration also inhibited the spontaneous nerve activity, but the magnitude of the inhibitory action was less than that of mexiletine. In another experiment, the afferent conductance velocity of the sural nerve was not affected after mexiletine was administrated in the WBN/Kob rats (62 weeks of age). The results suggest that pain mitigation of a diabetic prescribed with mexiletine may depend on the inhibitory effect of mexiletine on the generation of the spontaneous afferent action potentials by mexiletine in aged WBN/Kob rats, whereas mexiletine has no effect on the autonomic function of the afferent nerve.