title: Caffeine inhibits paresthesia induced by herpes simplex virus through action on primary sensory neurons in rats.
abstract: 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.
authors.affiliation: Department of Virology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan. kshiraki@ms.toyama-mpu.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Shiraki
authors.forename: T
authors.initials: T
authors.lastname: Andoh
authors.forename: M
authors.initials: M
authors.lastname: Imakita
authors.forename: M
authors.initials: M
authors.lastname: Kurokawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kuraishi
authors.forename: M
authors.initials: M
authors.lastname: Niimura
authors.forename: S
authors.initials: S
authors.lastname: Kageyama
mesh_terms: D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D017950:Ganglia, Sensory / Q000187:drug effects; D006561:Herpes Simplex / Q000503:physiopathology*; D018259:Herpesvirus 1, Human; D007150:Immunohistochemistry; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects; D010292:Paresthesia / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000998:Antiviral Agents; D000697:Central Nervous System Stimulants; D002110:Caffeine; D000212:Acyclovir