Intraperitoneal injection of thalidomide attenuates bone cancer pain and decreases spinal tumor necrosis factor-α expression in a mouse model.

Intraperitoneal injection of thalidomide attenuates bone cancer pain and decreases spinal tumor necrosis factor-α expression in a mouse model.
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DOI:
10.1186/1744-8069-6-64
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发表时间:
2010-10-05
期刊:
影响因子:
3.3
通讯作者:
Ma Z
Ma Z
中科院分区:
医学3区
文献类型:
--
作者:
Gu X;Zheng Y;Ren B;Zhang R;Mei F;Zhang J;Ma Z

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肿瘤坏死因子α (TNF-α)可能在炎性和神经性疼痛期间机械性异常痛和热痛觉过敏的发生中起关键作用。沙利度胺可选择性抑制TNF-α的产生。先前的研究表明,沙利度胺在各种疼痛模型中具有抗伤害性作用,但其对骨癌疼痛的作用尚未被研究。因此,在本研究中,我们在小鼠模型中研究了沙利度胺对骨癌诱导的痛觉过敏和上调脊髓TNF-α表达的影响。将骨肉瘤NCTC 2472细胞植入C3H/HeJ小鼠右侧股骨髓内腔,诱导持续的骨癌相关疼痛行为。术后第5、7、10、14天,荷瘤小鼠脊髓中TNF-α的表达明显高于假手术小鼠。术后第1天开始腹腔注射沙利度胺(50 mg/kg),此后每天1次,直至第7天,可减轻骨癌引起的机械性异常痛和热痛觉过敏以及脊髓中TNF-α的上调。结果表明,沙利度胺可有效缓解骨癌疼痛,可能是骨癌疼痛的一种有效的替代或辅助治疗方法。我们的数据还表明,脊柱TNF-α在骨癌疼痛的发展中的作用。
Tumor necrosis factor α (TNF-α) may have a pivotal role in the genesis of mechanical allodynia and thermal hyperalgesia during inflammatory and neuropathic pain. Thalidomide has been shown to selectively inhibit TNF-α production. Previous studies have suggested that thalidomide exerts anti-nociceptive effects in various pain models, but its effects on bone cancer pain have not previously been studied. Therefore, in the present study, we investigated the effect of thalidomide on bone cancer-induced hyperalgesia and up-regulated expression of spinal TNF-α in a mouse model. Osteosarcoma NCTC 2472 cells were implanted into the intramedullary space of the right femurs of C3H/HeJ mice to induce ongoing bone cancer related pain behaviors. At day 5, 7, 10 and 14 after operation, the expression of TNF-α in the spinal cord was higher in tumor-bearing mice compared to the sham mice. Intraperitoneal injection of thalidomide (50 mg/kg), started at day 1 after surgery and once daily thereafter until day 7, attenuated bone cancer-evoked mechanical allodynia and thermal hyperalgesia as well as the up-regulation of TNF-α in the spinal cord. These results suggest that thalidomide can efficiently alleviate bone cancer pain and it may be a useful alternative or adjunct therapy for bone cancer pain. Our data also suggest a role of spinal TNF-α in the development of bone cancer pain.
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