Pharmacological and Immunohistochemical Characterization of a Mouse Model of Acute Herpetic Pain

Abstract

We have recently found that the infection with herpes simplex virus type−1(HSV−1)of primary sensory neurons induces nociceptive hypersensitivity to noxious mechanical(hyperalgesia)and tactile stimulation(allodynia)in mice.In the present experiments, we determined the distribution of HSV−1 in the dorsal root ganglia and examined the effects of four analgesic agents on hyperalgesia and allodynia.HSV−1 was inoculated on the unilateral shin.HSV−antigen−positive cells were detected in the L4 and L5 dorsal root ganglia on days 5 and 7, but not day 3, post−inoculation.About 80% of the positive cells were small in size.Allodynia and hyperalgesia appeared on day 5 post−inoculation.Antinociceptive effects of analgesic agents were examined on day 6 post−inoculation.Morphine(1−5 mg/kg, subcutaneous)and gabapentin(10−100 mg/kg, peroral)dose−dependently inhibited both allodynia and hyperalgesia.Diclofenac(10−100 mg/kg, intraperitoneal)also produced antinociceptive effects, but there was a ceiling for the effect on hyperalgesia.Amitriptyline(3, 10 mg/kg, subcutaneous)did not affect allodynia and hyperalgesia.The results suggest that mechanical allodynia and hyperalgesia appeared when HSV−1 proliferated in the sensory neurons.This mouse model may be useful for studying the mechanisms of acute herpetic pain and anti−neuropathic pain agents.