Guo Liang-Hao, Schluesener Hermann J
Institute of Brain Research, University of Tuebingen, Calwer Str.3, 72076, Tuebingen, Germany.
Acta Neuropathol. 2006 Dec;112(6):703-13. doi: 10.1007/s00401-006-0135-z. Epub 2006 Sep 20.
We have analyzed development of mechanical hyperalgesia after repeated systemic lipopolysaccharide (LPS) injections and correlated these findings with stimulation of astrocytes and microglia in spinal cord. Male Lewis rats received a single or seven intraperitoneal injections of LPS. Mechanical hyperalgesia was measured as rat hindpaw withdrawal thresholds (PWTs). We observed that a single LPS injection elicited a specific change of PWTs while stimulated spinal glial activation was identified by immunoreactivities of specific markers, ED1, P2X4 receptor, endothelial monocyte activating polypeptide II (EMAP II) and glial fibrillary acidic protein (GFAP), respectively; multiple LPS treatments induced tolerance to mechanical hyperalgesia, whereas expression of ED1 and GFAP were further increased. In conclusion, we have demonstrated that the number of activated spinal glial cells was increased as an acute effect of LPS correlating with increased sensitivity to mechanical stimulation. However chronic exposure to LPS can develop a tolerance to mechanical hyperalgesia despite ongoing signs of CNS glial activation.
我们分析了反复全身注射脂多糖（LPS）后机械性痛觉过敏的发展情况，并将这些发现与脊髓中星形胶质细胞和小胶质细胞的刺激相关联。雄性Lewis大鼠接受单次或七次腹腔注射LPS。机械性痛觉过敏通过大鼠后爪缩足阈值（PWTs）来测量。我们观察到，单次注射LPS会引起PWTs的特定变化，同时分别通过特异性标志物ED1、P2X4受体、内皮单核细胞激活多肽II（EMAP II）和胶质纤维酸性蛋白（GFAP）的免疫反应性来确定脊髓胶质细胞的激活；多次LPS处理会诱导对机械性痛觉过敏的耐受性，而ED1和GFAP的表达进一步增加。总之，我们已经证明，作为LPS的急性效应，活化的脊髓胶质细胞数量增加与对机械刺激的敏感性增加相关。然而，尽管中枢神经系统胶质细胞持续激活，但长期接触LPS会对机械性痛觉过敏产生耐受性。
