Zhang Rui-Xin, Liu Bing, Wang Linbo, Ren Ke, Qiao Jian-Tian, Berman Brian M, Lao Lixing
Center For Integrative Medicine, School of Medicine, University of Maryland, 3rd Floor, James Kernan Hospital Mansion, 2200 Kernan Drive, Baltimore, MD 21207, USA.
Pain. 2005 Nov;118(1-2):125-36. doi: 10.1016/j.pain.2005.08.001. Epub 2005 Sep 9.
Studies suggest that astrocytes and microglia in the spinal cord are involved in the development of persistent pain induced by tissue inflammation and nerve injury. However, the role of glial cells in bone cancer pain is not well understood. The present study evaluated the spinal glial activation in a novel rat model of bone cancer pain produced by injecting AT-3.1 prostate cancer cells into the unilateral tibia of male Copenhagen rats. The structural damage to the tibia was monitored by radiological analysis. The thermal hyperalgesia, mechanical hyperalgesia and allodynia, and spontaneous flinch were measured. The results showed that: (1) inoculation of prostate cancer cells, but not the vehicle Hank's solution, induced progressive bone destruction at the proximal epiphysis of the tibia from day 7-20 post inoculation; (2) the inoculation also induced progressive thermal hyperalgesia, mechanical hyperalgesia, mechanical allodynia, and spontaneous flinches; (3) astrocytes and microglia were significantly activated in the spinal cord ipsilateral to the cancer leg, characterized by enhanced immunostaining of both glial fibrillary acidic protein (GFAP, astrocyte marker) and OX-42 (microglial marker); (4) IL-1beta was up-regulated in the ipsilateral spinal cord, evidenced by an increase of IL-1beta immunostained astrocytes. These results demonstrate that injection of AT-3.1 prostate cancer cells into the tibia produces progressive hyperalgesia and allodynia associated with the progression of tibia destruction, indicating the successful establishment of a novel male rat model of bone cancer pain. Further, bone cancer activates spinal glial cells, which may release IL-1beta and other cytokines and contribute to hyperalgesia.
研究表明，脊髓中的星形胶质细胞和小胶质细胞参与了由组织炎症和神经损伤引起的持续性疼痛的发展。然而，神经胶质细胞在骨癌疼痛中的作用尚未得到充分了解。本研究评估了通过向雄性哥本哈根大鼠的单侧胫骨注射AT-3.1前列腺癌细胞所建立的新型骨癌疼痛大鼠模型中的脊髓神经胶质细胞激活情况。通过放射学分析监测胫骨的结构损伤。测量热痛觉过敏、机械性痛觉过敏和异常性疼痛以及自发退缩反应。结果显示：（1）接种前列腺癌细胞，而非载体汉克氏溶液，在接种后第7至20天诱导胫骨近端骨骺处出现进行性骨质破坏；（2）接种还诱导了进行性热痛觉过敏、机械性痛觉过敏、机械性异常性疼痛和自发退缩反应；（3）在患癌侧的脊髓中，星形胶质细胞和小胶质细胞被显著激活，其特征是胶质纤维酸性蛋白（GFAP，星形胶质细胞标志物）和OX-42（小胶质细胞标志物）的免疫染色增强；（4）白细胞介素-1β（IL-1β）在同侧脊髓中上调，这通过IL-1β免疫染色的星形胶质细胞增多得以证明。这些结果表明，向胫骨注射AT-3.1前列腺癌细胞会产生与胫骨破坏进展相关的进行性痛觉过敏和异常性疼痛，表明成功建立了一种新型雄性大鼠骨癌疼痛模型。此外，骨癌激活脊髓神经胶质细胞，后者可能释放IL-1β和其他细胞因子并导致痛觉过敏。
