Jpn. J. Pharmacol. 83 (4), 319-326 (2000)

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

Ichiro Takasaki1, Tsugunobu Andoh1, Makoto Nitta1, Hiroki Takahata2, Hideo Nemoto2, Kimiyasu Shiraki3, Hiroshi Nojima1 and Yasushi Kuraishi1,*

1Department of Applied Pharmacology, 2Department of Organochemical Design and Synthesis, Faculty of Pharmaceutical Sciences,
3Department of Virology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
* To whom correspondence should be addressed.

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.

Keywords: Herpes simplex virus, Neuropathic pain, Morphine, Diclofenac, Gabapentin

Copyright© The Japanese Pharmacological Society 2000

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