Different roles of nitric oxide synthase-1 and -2 between herpetic and postherpetic allodynia in mice.
We investigated using the mice role of nitric oxide synthase (NOS) in the spinal dorsal horn in herpetic and postherpetic pain, especially allodynia, which was induced by transdermal inoculation of the hind paw with herpes simplex virus type-1 (HSV-1). The virus inoculation induced NOS2 expression in the lumbar dorsal horn of mice with herpetic allodynia, but not postherpetic allodynia. There were no substantial alternations in the expression level of NOS1 at the herpetic and postherpetic stages. Herpetic allodynia was significantly inhibited by i.p. administration of the selective NOS2 inhibitor S-methylisothiourea, but not the selective NOS1 inhibitor 7-nitroindazole. NOS2 expression was observed around HSV-1 antigen-immunoreactive cells. On the other hand, postherpetic allodynia was significantly inhibited by i.p. administration of 7-nitroindazole, but not S-methylisothiourea. The activity of reduced nicotinamide adenine dinucleotide phosphate diaphorase, an index of NOS1 activity, significantly increased in the laminae I and II of the lumbar dorsal horn of mice with postherpetic allodynia, but not mice without postherpetic allodynia. The expression level of NOS1 mRNA in the dorsal root ganglia was similar between mice with and without postherpetic allodynia. The results suggest that herpetic and postherpetic allodynia is mediated by nitric oxide in the dorsal horn and that NOS2 and NOS1 are responsible for herpetic and postherpetic allodynia, respectively. It may be worth testing the effects of NOS2 and NOS1 inhibitors on herpetic pain and postherpetic neuralgia in human subjects, respectively.
Sasaki
A
A
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Mabuchi
T
T
Serizawa
K
K
Takasaki
I
I
Andoh
T
T
Shiraki
K
K
Ito
S
S
Kuraishi
Y
Y
D000818:Animals; D008058:Dihydrolipoamide Dehydrogenase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005727:Ganglia, Spinal / Q000201:enzymology* / Q000503:physiopathology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000502:physiology; D006930:Hyperalgesia / Q000201:enzymology / Q000503:physiopathology / Q000821:virology; D007191:Indazoles / Q000494:pharmacology; D007550:Isothiuronium / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D051474:Neuralgia, Postherpetic / Q000201:enzymology* / Q000503:physiopathology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009619:Nociceptors / Q000201:enzymology / Q000503:physiopathology / Q000821:virology; D020671:Posterior Horn Cells / Q000201:enzymology* / Q000503:physiopathology / Q000821:virology; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D004791:Enzyme Inhibitors; D007191:Indazoles; D012333:RNA, Messenger; D007550:Isothiuronium; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D008058:Dihydrolipoamide Dehydrogenase; C027744:S-methylisothiopseudouronium; C080122:7-nitroindazole