Effect of mexiletine on fenvalerate-induced nociceptive response in diabetic mice

The effect of mexiletine on the nociceptive behavior induced by the intrathecal injection of fenvalerate, which predominantly activates tetrodotoxin-resistant (TTX-R) sodium channels, was studied in diabetic mice. The intrathecal injection of fenvalerate induced a characteristic behavioral syndrome that mainly consisted of reciprocal hind limb scratching directed toward caudal parts of the body and biting or licking of the hind legs in mice. The intensity of fenvalerate-induced nociceptive responses was significantly greater in diabetic mice than non-diabetic mice. This fenvalerate-induced behavior was dose-dependently inhibited by mexiletine (3-30 mg/kg, i.p.). Intrathecal pretreatment with fenvalerate produced thermal hyperalgesia and allodynia in the tail-flick test in naive mice. Furthermore, mexiletine at doses of 10 and 30 mg/kg, i.p., dose-dependently and significantly reduced fenvalerate-induced thermal hyperalgesia and allodynia in the tail-flick test in naive mice. These present data suggest that i.p. pretreatment with mexiletine produced dose-dependent inhibition of fenvalerate-induced hyperalgesia and allodynia in mice, especially diabetic mice. This effect may be, at least in part, mediated by the inhibition of TTX-R sodium channel-mediated nociceptive transmission in the spinal cord.