Tanga F Y, Raghavendra V, Nutile-McMenemy N, Marks A, Deleo J A
Department of Anesthesiology, Dartmouth Medical School, Lebanon, NH 03756, USA.
Neuroscience. 2006 Jul 7;140(3):1003-10. doi: 10.1016/j.neuroscience.2006.02.070.
S100beta is a calcium-binding peptide produced mainly by astrocytes that exerts paracrine and autocrine effects on neurons and glia. We have previously shown that S100beta is markedly elevated at the mRNA level in the spinal cord following peripheral inflammation, intraplantar administration of complete Freund's adjuvant in the rat. The purpose of the present study was to further investigate the role of astrocytic S100beta in mediating behavioral hypersensitivity in rodent models of persistent pain. First, we assessed the lumbar spinal cord expression of S100beta at the mRNA and protein level using real-time RT-PCR, Western blot and immunohistochemistry analysis following L5 spinal nerve transection in rats, a rodent model of neuropathic pain. Second, we assessed behavioral hypersensitivity (mechanical allodynia) in wild type and genetically modified mice lacking or overexpressing S100beta following L5 spinal nerve transection. Third, we assessed the expression level of S100beta protein in the CD1 wild type mice after nerve injury. We report that lumbar spinal S100beta mRNA steadily increased from days 4-28 after nerve injury. S100beta protein in the lumbar spinal cord was significantly increased in both rats and mice at day 14 following nerve injury as compared with sham control groups. S100beta genetically deficient mice displayed significantly increased tactile thresholds (reduced response to non-noxious stimuli) after nerve injury as compared with the wild type group. S100beta overexpressing mice displayed significantly decreased tactile threshold responses (enhanced response to non-noxious stimuli). Together, these results from both series of experiments using a peripheral nerve injury model in two different species implicate the involvement of glial-derived S100beta in the pathophysiology of neuropathic pain.
S100β是一种主要由星形胶质细胞产生的钙结合肽，对神经元和神经胶质细胞发挥旁分泌和自分泌作用。我们之前已经表明，在大鼠足底注射完全弗氏佐剂引发外周炎症后，脊髓中S100β的mRNA水平显著升高。本研究的目的是进一步探讨星形胶质细胞来源的S100β在介导持续性疼痛啮齿动物模型行为超敏反应中的作用。首先，我们在大鼠L5脊髓神经横断（一种神经性疼痛的啮齿动物模型）后，使用实时逆转录聚合酶链反应、蛋白质免疫印迹和免疫组织化学分析，评估了S100β在腰段脊髓的mRNA和蛋白质水平表达。其次，我们评估了野生型和缺乏或过表达S100β的基因修饰小鼠在L5脊髓神经横断后的行为超敏反应（机械性异常性疼痛）。第三，我们评估了神经损伤后CD-1野生型小鼠中S100β蛋白的表达水平。我们报告，腰段脊髓S100β mRNA在神经损伤后第4天至28天稳步增加。与假手术对照组相比，神经损伤后第14天，大鼠和小鼠腰段脊髓中的S100β蛋白均显著增加。与野生型组相比，S100β基因缺陷小鼠在神经损伤后表现出显著升高的触觉阈值（对非伤害性刺激的反应降低）。过表达S100β的小鼠表现出显著降低的触觉阈值反应（对非伤害性刺激的反应增强）。总之，这两个系列实验在两个不同物种中使用外周神经损伤模型所得到的结果表明，神经胶质细胞来源的S100β参与了神经性疼痛的病理生理过程。
