演題番号 : S3-1-1-4
倉石 泰 / Yasushi Kurashi:1
1:富山大学 大学院医学薬学研究部 応用薬理学研究室 / Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama
Reactivation of human herpesvirus 3 in the sensory ganglion causes herpes zoster, which is characterized by severe pain, including allodynia, and often leads to postherpetic neuralgia. Mouse model of herpetic pain and postherpetic neuralgia is made by transdermal inoculation with human herpesvirus 1. The virus actively replicated in the sensory ganglion around day 5 after the inoculation and vesicle eruption in the inoculated dermatome was on day 5. Allodynia of the affected dermatomes started a few days before the eruption. Dynamic allodynia (pain due to brush strokes) was more marked than was static allodynia (pain due to punctate stimulation with fine von Frey filament). Responses of the tibial nerve to mechanical (brush, punctum, pinch) stimuli were all reduced in herpetic mice. The excitatory response of wide-dynamic range neurons in the dorsal horn to brush, but neither punctum nor pinch, stimulation was increased in herpetic mice. In mice with postherpetic neuralgia, unmyelinated and myelinated axons were injured markedly and partly, respectively, in the affected sciatic nerve. The intensity of dynamic allodynia inversely correlated with the reduction in behavioral response to capsaicin injection and heat stimulation. Regarding P2X purinergic receptors in the dorsal horn, P2X4 mRNA increased from 5 to 7 days after inoculation and slight increase was observed at the postherpetic stage, whereas P2X7 mRNA increased from 7 to at least 30 days after inoculation. P2X7-like immunoreactivity was present in neurons and astrocytes. The P2X7 receptor antagonists partially but significantly suppressed dynamic and static allodynia. Taken together, this mouse model of herpetic and postherpetic pain is suggested to be C-fiber deafferentation type and P2X7 receptors may play a role in allodynia.