Different roles of nitric oxide synthase-1 and -2 between herpetic and postherpetic allodynia in mice

• Published in: Neuroscience Vol. 150; no. 2; pp. 459 - 466
• Main Authors: Sasaki, A, Mabuchi, T, Serizawa, K, Takasaki, I, Andoh, T, Shiraki, K, Ito, S, Kuraishi, Y
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 05-12-2007; Elsevier
• Subjects: Animals; Biological and medical sciences; Dihydrolipoamide Dehydrogenase - metabolism; dorsal horn; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Female; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - enzymology; Ganglia, Spinal - physiopathology; Ganglia, Spinal - virology; Herpes simplex virus 1; herpes zoster; Herpesvirus 1, Human - physiology; Hyperalgesia - enzymology; Hyperalgesia - physiopathology; Hyperalgesia - virology; Indazoles - pharmacology; Isothiuronium - analogs & derivatives; Isothiuronium - pharmacology; Mice; Mice, Inbred C57BL; Neuralgia, Postherpetic - enzymology; Neuralgia, Postherpetic - physiopathology; Neurology; Nitric Oxide - biosynthesis; nitric oxide synthase isoenzymes; Nitric Oxide Synthase Type I - antagonists & inhibitors; Nitric Oxide Synthase Type I - genetics; Nitric Oxide Synthase Type I - metabolism; Nitric Oxide Synthase Type II - antagonists & inhibitors; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Nociceptors - enzymology; Nociceptors - physiopathology; Nociceptors - virology; Posterior Horn Cells - enzymology; Posterior Horn Cells - physiopathology; Posterior Horn Cells - virology; postherpetic neuralgia; primary sensory nerve; RNA, Messenger - metabolism; Up-Regulation - physiology; Vertebrates: nervous system and sense organs; NADPH; NO; primary sensory nerve; dorsal horn; 7-NI; phosphate-buffered saline; L; HSV-1; TBS-T; S; nitric oxide synthase isoenzymes; 7-nitroindazole; glyceraldehyde-3-phosphate dehydrogenase; nitric oxide synthase; S-methylisothiourea sulfate; lumbar; PBS; nitric oxide; herpes zoster; nicotinamide adenine dinucleotide phosphate; qRT-PCR; Tris-buffered saline containing Tween; sacral; herpes simplex virus type-1; NOS; postherpetic neuralgia; quantitative reverse transcription-polymerase chain reaction; SMT; GAPDH; Allodynia; Spinal cord; Enzyme; Rodentia; Central nervous system; Posterior spinal horn; Nitric-oxide synthase; Vertebrata; Mammalia; Mouse; Animal; Sensory nerve; Oxidoreductases
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2007.09.067

Abstract 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.