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 infect ion with herpes simplex virus type-1 (HSV-1) induces allodynia and hyperalg esia in mice. When HSV-1 was inoculated on the hind paw of the mouse, erupt ion appeared on the back on day 5 postinoculation and zosteriform skin lesi ons were developed on the inoculated side. Allodynia and hyperalgesia becam e apparent in the hind paw on the inoculated side on day 5 and persisted un til at least day 8. HSV-1 DNA was detected in the dorsal root ganglia from days 2 to 8 postinoculation, with a peak effect on day 5. The application o f heat-inactivated HSV-1 induced no allodynia, hyperalgesia and skin lesion . When started from days 0 or 2, repeated treatment with acyclovir, anti-HS V-1 agent, inhibited the appearance of allodynia, hyperalgesia, eruption an d the viral proliferation in the dorsal root ganglia. In contrast, when sta rted from days 5 or 6, acyclovir treatment slightly inhibited the developme nt of skin lesions and the viral proliferation, but not allodynia and hyper algesia. 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. (C) 2000 International Associatio n for the Study of Pain. Published by Elsevier Science B.V. All rights rese rved.