Attenuating effect of mexiletine hydrochloride on herpetic pain in mice infected with herpes simplex virus.
The influence of mexiletine hydrochloride on herpes-related pain responses was examined using mice infected with herpes virus. BALB/c mice were inoculated with herpes simplex virus (HSV; 1 x 10(6) plaque-forming units) on the right hind paw, and the contralateral hind paw was without inoculation. The changes in nociceptive threshold were examined using electric von fray meter. BALB/c mice inoculated with HSV showed a decrease in nociceptive threshold. Intraperitoneal administration of mexiletine prevented the decrease in nociceptive threshold dose-dependently in HSV-inoculated mice, which was firstly observed at a dose of 15.0 mg kg(-1), and peaked at doses more than 17.5 mg kg(-1). This antinociceptive effect of mexiletine attained peaks at 60-90 min after administration and declined gradually to non-treated levels by 150 min. Intraperitoneal administration of mexiletine at a dose of 17.5 mg kg(-1) (but not 10.0 mg kg(-1)) caused significant increase in beta-endorphin levels in the mid brain and hypothalamus of HSV-inoculated mice. However, mexiletine scarcely affected noradrenaline (norepinephrine) levels in the pons and medulla oblongata, even when HSV-inoculated mice were treated with 17.5 mg kg(-1) mexiletine. These results strongly suggested that mexiletine exerts antinociceptive effects on herpes-related pain through enhancement of beta-endorphin levels in the central nervous system in HSV-inoculated mice. It is also suggested that mexiletine will be a good candidate for an antinociceptive drug in the treatment of acute herpetic pain in man.
Asano
Kazuhito
K
Department of Physiology, School of Medicine, Showa University, Hatanodai, Tokyo, Japan. asanok@med.showa-u.ac.jp
Sameshima
Tatsuo
T
Shirasawa
Hiroshi
H
Hisamitsu
Tadashi
T
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006561:Herpes Simplex / Q000150:complications*; D007263:Infusions, Parenteral; D008801:Mexiletine / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010146:Pain / Q000188:drug therapy* / Q000821:virology*; D017288:Pain Threshold / Q000187:drug effects; D018139:Simplexvirus / Q000472:pathogenicity
D000889:Anti-Arrhythmia Agents; D008801:Mexiletine