Effects of the suppression of acute herpetic pain by gabapentin and amitriptyline on the incidence of delayed postherpetic pain in mice.
The inoculation of mice with herpes simplex virus type-1 (HSV-1) causes herpes zoster-like skin lesions and pain-related responses (tactile allodynia and mechanical hyperalgesia) from day 5 after inoculation. Skin lesions completely heal by day 15 after inoculation, but about half of mice with acute herpetic pain show pain-related responses long after the lesions heal. Using this mouse model, we examined the effects of repeated administration of gabapentin and amitriptyline on the acute herpetic pain and the incidence of postherpetic pain. Gabapentin and amitriptyline were administered three times daily from day 5 to 11 after inoculation. Postherpetic pain-related responses were assessed on day 30 after inoculation. Gabapentin (10-100 mg/kg) produced the dose-dependent inhibition of acute herpetic pain-related responses. This medication produced marked reduction in the incidence of delayed postherpetic pain and the dose of 100 mg/kg produced the complete inhibition. Amitriptyline (10 mg/kg) did not affect the acute pain-related responses in the initial 3- and 2-day periods and then gradually inhibited them. This dosage produced a substantial but non-significant decrease in the incidence of postherpetic pain-related responses. Amitriptyline (1 and 3 mg/kg) was without effects on acute herpetic and postherpetic pain-related responses. The results strongly support the idea that the severity of the acute herpetic pain is a risk factor of postherpetic neuralgia. It may be worth testing the effects of gabapentin on acute herpetic pain and the incidence of postherpetic neuralgia in human subjects.
Kuraishi
Yasushi
Y
Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan. kiraisiy@ms.toyama-mpu.ac.jp
Takasaki
Ichiro
I
Nojima
Hiroshi
H
Shiraki
Kimiyasu
K
Takahata
Hiroki
H
D000085:Acetates / Q000008:administration & dosage / Q000627:therapeutic use*; D000588:Amines; D000639:Amitriptyline / Q000008:administration & dosage / Q000627:therapeutic use*; D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D003509:Cyclohexanecarboxylic Acids; D004195:Disease Models, Animal; D005260:Female; D000077206:Gabapentin; D006561:Herpes Simplex / Q000150:complications*; D018259:Herpesvirus 1, Human; D051379:Mice; D008807:Mice, Inbred BALB C; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010812:Physical Stimulation; D013997:Time Factors; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D000639:Amitriptyline; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin