Allodynia and hyperalgesia induced by herpes simplex virus type-1 infection in mice.
Human subjects infected with herpes or varicella-zoster viruses complain of pain, such as allodynia, in or near the region with vesicles. However, the mechanisms of the pain are unclear. We show for the first time that infection with herpes simplex virus type-1 (HSV-1) induces allodynia and hyperalgesia in mice. When HSV-1 was inoculated on the hind paw of the mouse, eruption appeared on the back on day 5 post-inoculation, and zosteriform skin lesions were developed on the inoculated side. Allodynia and hyperalgesia became apparent in the hind paw on the inoculated side on day 5 and persisted until at least day 8. HSV-1 DNA was detected in the dorsal root ganglia from days 2 to 8 post-inoculation, with a peak effect on day 5. The application of heat-inactivated HSV-1 induced no allodynia, hyperalgesia and skin lesion. When started from days 0 or 2, repeated treatment with acyclovir, anti-HSV-1 agent, inhibited the appearance of allodynia, hyperalgesia, eruption and the viral proliferation in the dorsal root ganglia. In contrast, when started from days 5 or 6, acyclovir treatment slightly inhibited the development of skin lesions and the viral proliferation, but not allodynia and hyperalgesia. These results suggest that the propagation of HSV-1 in the dorsal root ganglia produces allodynia and hyperalgesia as a result of functional abnormality of the sensory neurons in mice. This may be a useful model for studying the mechanisms of herpetic pain.
Takasaki
I
I
Department of Applied Pharmacology, Toyama Medical and Pharmaceutical University, Japan.
Andoh
T
T
Shiraki
K
K
Kuraishi
Y
Y
D000212:Acyclovir / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D001522:Behavior, Animal / Q000502:physiology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005727:Ganglia, Spinal / Q000503:physiopathology / Q000821:virology; D006561:Herpes Simplex / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D018259:Herpesvirus 1, Human; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010146:Pain / Q000188:drug therapy / Q000209:etiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000473:pathology
D000998:Antiviral Agents; D004279:DNA, Viral; D000212:Acyclovir