Sasaki A, Mabuchi T, Serizawa K, Takasaki I, Andoh T, Shiraki K, Ito S, Kuraishi Y
Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Neuroscience. 2007 Dec 5;150(2):459-66. doi: 10.1016/j.neuroscience.2007.09.067. Epub 2007 Oct 9.
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.
我们研究了一氧化氮合酶（NOS）在小鼠脊髓背角在疱疹性及疱疹后疼痛（尤其是异常性疼痛）中的作用，该疼痛由将1型单纯疱疹病毒（HSV-1）经皮接种到后爪诱发。病毒接种在患有疱疹性异常性疼痛的小鼠腰段背角诱导了NOS2表达，但在疱疹后异常性疼痛的小鼠中未诱导。在疱疹性及疱疹后阶段，NOS1的表达水平没有实质性变化。腹腔注射选择性NOS2抑制剂S-甲基异硫脲可显著抑制疱疹性异常性疼痛，但选择性NOS1抑制剂7-硝基吲唑则不能。在HSV-1抗原免疫反应性细胞周围观察到NOS2表达。另一方面，腹腔注射7-硝基吲唑可显著抑制疱疹后异常性疼痛，但S-甲基异硫脲则不能。还原型烟酰胺腺嘌呤二核苷酸磷酸黄递酶的活性（NOS1活性指标）在患有疱疹后异常性疼痛的小鼠腰段背角I层和II层中显著增加，但在没有疱疹后异常性疼痛的小鼠中则没有。在患有和没有疱疹后异常性疼痛的小鼠之间，背根神经节中NOS1 mRNA的表达水平相似。结果表明，疱疹性及疱疹后异常性疼痛由背角中的一氧化氮介导，且NOS2和NOS1分别负责疱疹性及疱疹后异常性疼痛。分别测试NOS2和NOS1抑制剂对人类疱疹性疼痛和疱疹后神经痛的影响可能是值得的。
