Caffeine inhibits paresthesia induced by herpes simplex virus through action on primary sensory neurons in rats

Herpetic infection causes paresthesia, including hypoalgesia, in humans and hypoalgesia in rats. This study was conducted to examine the effect of caffeine, which inhibits replication of herpes simplex virus type-1 (HSV) and affects several neuronal functions, on HSV-induced paresthesia in rats. HSV-induced hypoalgesia was suppressed by repeated treatment of unilateral hindpaw with 10% caffeine gel regardless of when the treatment was started. Repeated treatment with acyclovir, an anti-HSV agent, suppressed HSV-induced hypoalgesia only when started before inoculation; acyclovir did not produce therapeutic effects on the HSV-induced sensory abnormality. Many dorsal root ganglion neurons were positive for HSV antigen following HSV inoculation of the hindpaw. Repeated treatment with caffeine and acyclovir markedly decreased HSV antigen-positive neurons in the dorsal root ganglia when started before, but not 2 or 4 days after, infection. These results suggest that topical caffeine inhibited HSV-induced paresthesia through direct action on sensory neurons, and that not only antiviral activity but also direct alteration of neural functions are involved in the caffeine sensory actions.