Effects of analgesics on delayed postherpetic pain in mice.
BACKGROUND
Postherpetic neuralgia is pain that persists long after the disappearance of the cutaneous lesions of herpes zoster. However, the mechanisms of this delayed pain are unclear. Herpes simplex virus infection induces cutaneous lesions and pain-related responses in mice. The authors examined whether such responses would persist after the disappearance of the cutaneous lesions and whether some analgesics would be effective against them.


METHODS
Female BALB/c mice were inoculated with herpes simplex virus type 1 on the unilateral hind paw. Pain-related responses of hind paw were determined using von Frey filaments. Beginning 5 days after inoculation, mice were given perorally the antiherpes agent acyclovir five times a day for 7 days. Effects of morphine (3-5 mg/kg subcutaneously), gabapentin (30-100 mg/kg perorally), mexiletine (10-30 mg/kg intraperitoneally), and diclofenac (30 mg/kg intraperitoneally) on pain-related responses were examined on days 25-35 after inoculation.


RESULTS
Viral inoculation induced cutaneous lesions and pain-related responses beginning on day 5 after inoculation. Acyclovir treatment healed all skin lesions by day 15 after inoculation. Approximately half of the mice given acyclovir showed pain-related responses at least until day 40 after inoculation. Morphine, gabapentin, and mexiletine dose-dependently inhibited pain-related responses, but diclofenac had no effects.


CONCLUSIONS
The authors show a mouse model of delayed postherpetic pain. This may be useful for manifesting the mechanisms of postherpetic neuralgia and the factors contributing to the transition from acute herpetic pain to delayed postherpetic pain. This may also be useful for the development of new analgesics against postherpetic neuralgia.
Takasaki
Ichiro
I
Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Sasaki
Atsushi
A
Andoh
Tsugunobu
T
Nojima
Hiroshi
H
Shiraki
Kimiyasu
K
Kuraishi
Yasushi
Y
D000085:Acetates / Q000627:therapeutic use; D000208:Acute Disease; D000212:Acyclovir / Q000627:therapeutic use; D000588:Amines; D000700:Analgesics / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D000077206:Gabapentin; D006566:Herpesviridae Infections / Q000150:complications* / Q000821:virology; D018259:Herpesvirus 1, Human; D008801:Mexiletine / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy* / Q000209:etiology* / Q000523:psychology; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000700:Analgesics; D000701:Analgesics, Opioid; D000998:Antiviral Agents; D003509:Cyclohexanecarboxylic Acids; D004279:DNA, Viral; D008801:Mexiletine; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine; D000212:Acyclovir