Dose-related antiallodynic effects of cyclic AMP response element-binding protein-antisense oligonucleotide in the spared nerve injury model of neuropathic pain
Dose-related antiallodynic effects of cyclic AMP response element-binding protein-antisense oligonucleotide in the spared nerve injury model of neuropathic pain
复制标题
DOI：
10.1016/j.neuroscience.2006.01.011
复制
发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Li, Y. -Q.
中科院分区：
文献类型：
--
作者：
Wang, Y. -Y.;Wu, S. -X.;Li, Y. -Q.
一种被称为cAMP反应元件结合蛋白的转录因子已被证明参与了神经病理性疼痛和炎症性疼痛的中枢敏化。本研究探讨了cAMP反应元件结合蛋白和磷酸化的cAMP反应元件结合蛋白在维持神经病理性疼痛模型“备用神经损伤”所致的机械性和冷性痛觉异常中的作用。首先，免疫组织化学研究结果显示，备用神经损伤后14天脊髓背角中磷酸化的环AMP反应元件结合蛋白增加，而不是cAMP反应元件结合蛋白，提示磷酸化的环AMP反应元件结合蛋白可能在备用神经损伤中起作用。鞘内注射环磷酸腺苷反应元件结合蛋白反义寡核苷酸10mU/d、20mU/d和40mU/d共5天，结果表明，与正义寡核苷酸和低剂量(10mU/g)相比，高剂量(20和40mU g)对机械性(双侧)和寒性(同侧)痛觉均有明显的缓解作用。Western印迹结果显示，行为行为强度的减轻伴随着脊髓背角中总的环AMP反应元件结合蛋白和磷酸化的环AMP反应元件结合蛋白的显着减少。此外，同侧和对侧背角的环AMP反应元件结合蛋白和磷酸化的环AMP反应元件结合蛋白也没有差异。我们的研究结果表明，脊髓后角行为超敏反应的表达与环磷酸腺苷反应元件结合蛋白的激活密切相关，这支持了磷酸化的环磷酸腺苷反应元件结合蛋白可能在慢性神经病理性疼痛的维持中起重要作用的观点。(C)2006年由爱思唯尔有限公司代表IBRO出版。
A transcription factor known as cyclic AMP response element-binding protein has been shown to be involved in the central sensitization in neuropathic pain and inflammation pain. The present study examined the roles of cyclic AMP response element-binding protein and of the phosphorylated cyclic AMP response element-binding protein in the maintenance of mechanical and cold allodynia induced by a neuropathic pain model, "spared nerve injury," in rats. First, the results of immunohistochemical study showed that phosphorylated cyclic AMP response element-binding protein, but not cyclic AMP response element-binding protein, increased bilaterally in the spinal dorsal horn 14 days following spared nerve injury, indicating a possible contribution of phosphorylated cyclic AMP response element-binding protein in spared nerve injury. Second, chronic intrathecal application of cyclic AMP response element-binding protein antisense oligodeoxynucleotide with three doses (10 mu g/day, 20 mu g/day and 40 mu g/day) for 5 days demonstrated that the higher doses (20 and 40 mu g) significantly attenuated both mechanical (bilaterally) and cold (ipsilaterally) allodynia, compared with sense oligodeoxynucleotide and the lower dose (10 mu g). Western blot results showed that the alleviation in intensity of behavioral performance was accompanied by a significant reduction of total cyclic AMP response element-binding protein and phosphorylated cyclic AMP response element-binding protein in the spinal dorsal horn. Moreover, there were no differences in cyclic AMP response element-binding protein and phosphorylated cyclic AMP response element-binding protein between ipsilateral and contralateral dorsal horns. Our data demonstrate a close association between the expression of behavioral hypersensitivity and cyclic AMP response element-binding protein activation in the spinal dorsal horn following spared nerve injury, supporting the notion that phosphorylated cyclic AMP response element-binding protein may play an important role in the maintenance of chronic neuropathic pain. (c) 2006 Published by Elsevier Ltd on behalf of IBRO.