Pharmacological and immunohistochemical characterization of a mouse model of acute herpetic pain.
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.
Takasaki
I
I
Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Andoh
T
T
Nitta
M
M
Takahata
H
H
Nemoto
H
H
Shiraki
K
K
Nojima
H
H
Kuraishi
Y
Y
D000085:Acetates / Q000627:therapeutic use*; D000588:Amines; D000639:Amitriptyline / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000927:Anticonvulsants / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use*; D003509:Cyclohexanecarboxylic Acids; D004008:Diclofenac / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D000077206:Gabapentin; D005727:Ganglia, Spinal / Q000821:virology; D006561:Herpes Simplex / Q000188:drug therapy*; D018259:Herpesvirus 1, Human; D006930:Hyperalgesia / Q000188:drug therapy / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009020:Morphine / Q000627:therapeutic use; D009437:Neuralgia / Q000188:drug therapy / Q000821:virology; D009475:Neurons, Afferent / Q000821:virology; D010146:Pain / Q000188:drug therapy* / Q000821:virology; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000927:Anticonvulsants; D000929:Antidepressive Agents, Tricyclic; D003509:Cyclohexanecarboxylic Acids; D004008:Diclofenac; D000639:Amitriptyline; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009020:Morphine