Ichiro Takasaki1, Tsugunobu Andoh1, Makoto Nitta1,
Hiroki Takahata2, Hideo Nemoto2, Kimiyasu Shiraki3,
Hiroshi Nojima1 and Yasushi Kuraishi1,*
1Departmentﾊof Applied Pharmacology, 2Departmentﾊof
Organochemical Design and Synthesis, Faculty of Pharmaceutical Sciences,
3Departmentﾊ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ﾊ5 and 7, but not dayﾊ3, post-inoculation. About 80% of the
positive cells were small in size. Allodynia and hyperalgesia appeared on
dayﾊ5 post-inoculation. Antinociceptive effects of analgesic agents were
examined on dayﾊ6 post-inoculation. Morphine (1-5ﾊmg/kg, subcutaneous) and
gabapentin (10-100ﾊmg/kg, peroral) dose-dependently inhibited both allodynia
and hyperalgesia. Diclofenac (10-100ﾊmg/kg, intraperitoneal) also produced
antinociceptive effects, but there was a ceiling for the effect on hyperalgesia.
Amitriptyline (3, 10ﾊ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ｩ The Japanese Pharmacological Society 2000
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