Division of Molecular Genetics Research, Life Science Research Center, University of Toyama, Toyama, Japan Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan Department of Pharmacology, School of Pharmaceutical Sciences, Ohu University, Koriyama, Fukushima, Japan Department of Virology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan Department of Dermatology, University of California, Davis, School of Medicine, Sacramento, CA, USA Department of Biology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Pain. 2012 Mar;153(3):585-592. doi: 10.1016/j.pain.2011.11.022. Epub 2011 Dec 24.
To identify endogenous factors involved in herpetic pain, we performed genome-wide microarray analysis of the spinal cord of mice that suffered from herpetic allodynia induced by inoculation with herpes simplex virus type 1, which revealed marked induction of galectin-3, a β-galactoside-binding lectin. Therefore, we investigated the role of galectin-3 in herpetic allodynia. The expression levels of galectin-3 mRNA and protein were increased with a temporal pattern similar to that of herpetic allodynia. Galectin-3-expressing cells were mainly localized in the superficial dorsal horn, round in shape, and positive for the macrophage/microglia markers Iba-1 and F4/80. In the deep dorsal horn, there were Iba-1-positive cells with ramified and stout processes, which were negative for galectin-3. In the superficial dorsal horn, there were many CD3-positive T cells, but most of the galectin-3-expressing cells were negative for CD3. Galectin-3-expressing cells were negative for the neuronal marker NeuN and the astrocyte marker glial fibrillary acidic protein antibody. Deficiency in galectin-3 markedly reduced herpetic allodynia, without showing an effect on herpes zoster-like skin lesions. Intrathecal injection of galectin-3 produced mechanical allodynia in naive mice, and intrathecal injections of anti-galectin-3 antibodies significantly reduced herpetic allodynia. The present results suggest that galectin-3 in infiltrating macrophages and/or resident microglia in the spinal dorsal horn contributes to herpetic allodynia. Galectin-3 may be a new therapeutic target for the treatment of herpes zoster-associated pain.
为了鉴定与疱疹性疼痛相关的内源性因子，我们对感染单纯疱疹病毒 1 后出现疱疹性痛觉过敏的小鼠脊髓进行了全基因组微阵列分析，结果显示半乳糖凝集素-3（一种β-半乳糖苷结合凝集素）明显被诱导。因此，我们研究了半乳糖凝集素-3在疱疹性痛觉过敏中的作用。半乳糖凝集素-3 mRNA 和蛋白的表达水平呈时间依赖性增加，与疱疹性痛觉过敏的发生模式相似。半乳糖凝集素-3 表达细胞主要定位于脊髓背角浅层，呈圆形，巨噬细胞/小胶质细胞标志物 Iba-1 和 F4/80 阳性。在脊髓背角深层，有 Iba-1 阳性的细胞，其突起呈分支状且粗壮，为半乳糖凝集素-3 阴性。在脊髓背角浅层，有许多 CD3 阳性 T 细胞，但大多数半乳糖凝集素-3 表达细胞 CD3 阴性。半乳糖凝集素-3 表达细胞神经元标志物 NeuN 和星形胶质细胞标志物胶质纤维酸性蛋白抗体阴性。半乳糖凝集素-3 缺乏显著减轻疱疹性痛觉过敏，但对半节段性带状疱疹样皮肤损伤无影响。鞘内注射半乳糖凝集素-3 可在未处理的小鼠中引起机械性痛觉过敏，鞘内注射抗半乳糖凝集素-3 抗体可显著减轻疱疹性痛觉过敏。这些结果表明，脊髓背角浸润的巨噬细胞和/或固有小胶质细胞中的半乳糖凝集素-3 参与了疱疹性痛觉过敏。半乳糖凝集素-3 可能是治疗带状疱疹相关疼痛的新治疗靶点。
