Vol. 296, Issue 2, 270-275, February 2001

Gabapentin Antinociception in Mice with Acute Herpetic Pain Induced by Herpes Simplex Virus Infection

Ichiro Takasaki, Tsugunobu Andoh, Hiroshi Nojima, Kimiyasu Shiraki and Yasushi Kuraishi

Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences (I.T., H.N., Y.K.) and Department of Virology, Faculty of Medicine (K.S.), Toyama Medical and Pharmaceutical University, Toyama, Japan; and National Heart, Lung, and Blood Institute, National Institute of Health, Bethesda, Maryland (T.A.)

The effects of systemic and local injections of gabapentin, a novel anticonvulsant agent, were tested on nociceptive behaviors in mice with acute herpetic pain. Transdermal infection with herpes simplex virus type-1 (HSV-1) produced nociceptive hypersensitivity of the infected hind paw to innocuous (allodynia) and noxious mechanical stimulation (hyperalgesia) with von Frey filaments. Systemic administration of gabapentin (10-100 mg/kg, peroral) produced a dose-dependent inhibition of both allodynia and hyperalgesia; gabapentin (30-300 mg/kg) did not affect locomotor activity. Intrathecal injection of gabapentin (10-100 µg/animal) also attenuated dose dependently both nociceptive hypersensitivities. In contrast, intraplantar, intracisternal, and intracerebroventricular administration of gabapentin (10-100 µg/animal) had no effect on the HSV-1-induced nociceptive hypersensitivities. Pretreatment with naltrexone (1 mg/kg) inhibited antinociceptive effect of morphine (5 mg/kg), but not gabapentin (100 mg/kg). Repeated administration of morphine (5 mg/kg, four times) led to tolerance of antinociceptive action, whereas gabapentin (100 mg/kg, four times) had antinociceptive effect even after the forth administration. The present results suggest that gabapentin is effective in the treatment of acute herpetic pain without apparent adverse effects, and analgesic action of gabapentin is mainly mediated by actions on the spinal cord.