Remote astrocytic and microglial activation modulates neuronal hyperexcitability and below-level neuropathic pain after spinal injury in rat.
Remote astrocytic and microglial activation modulates neuronal hyperexcitability and below-level neuropathic pain after spinal injury in rat.
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DOI：
10.1016/j.neuroscience.2009.03.055
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发表时间：
2009-07-07
期刊：
影响因子：
3.3
通讯作者：
Hulsebosch, C. E.
中科院分区：
文献类型：
--
作者：
Gwak, Y. S.;Hulsebosch, C. E.
在这项研究中，我们评估了星形细胞和小胶质细胞激活是否介导脊髓损伤后的低水平神经性疼痛。雄性Sprague-Dawley大鼠（225-250 g）给予低胸（T13）脊柱横切面半切，采用行为学、电生理和免疫组织化学方法观察低水平神经性疼痛的发生和维持。术后第28天，与假手术对照组相比，两后肢的足爪戒断阈值和热潜伏期显著降低，脊髓背角两侧腰椎（L4-5）脊髓宽动态范围（WDR）神经元的高兴奋性显著降低（*p<0.05）。脊髓损伤后立即连续7天使用丙烯茶碱（PPF, 10 mM）鞘内治疗，与载药治疗相比，两后肢机械性异常痛和热痛觉过敏的发生呈剂量相关减少（*p<0.05）。脊髓损伤后28天鞘内单次注射PPF，可减轻两后肢已有的机械异常痛和热痛觉过敏，且呈剂量相关减少（*p<0.05）。在电生理学研究中，在脊髓表面局部处理10mm PPF可减弱神经元对机械刺激的过度兴奋性。在免疫组化研究中，与假对照相比，脊髓半切除大鼠的星形胶质细胞和小胶质细胞在腰椎背角的浅背角和深背角中GFAP和OX-42的表达均显著增加（*p<0.05）， PPF以剂量相关的方式阻止了这种表达（p<0.05）。总之，我们目前的数据支持星形细胞和小胶质细胞激活有助于脊髓损伤后中枢神经性疼痛。
In this study, we evaluated whether astrocytic and microglial activation mediates below-level neuropathic pain following spinal cord injury. Male Sprague-Dawley (225–250 g) rats were given low thoracic (T13) spinal transverse hemisection and behavioral, electrophysiological and immunohistochemical methods were used to examine the development and maintenance of below-level neuropathic pain. On post operation day 28, both hindlimbs showed significantly decreased paw withdrawal thresholds and thermal latencies as well as hyperexcitability of lumbar (L4-5) spinal wide dynamic range (WDR) neurons on both sides of spinal dorsal horn compared to sham controls (*p<0.05). Intrathecal treatment with propentofylline (PPF, 10 mM) for 7 consecutive days immediately after spinal injury attenuated the development of mechanical allodynia and thermal hyperalgesia in both hindlimbs in a dose related reduction compared to vehicle treatments (*p<0.05). Intrathecal treatment with single injections of PPF at 28 days after spinal injury, attenuated the existing mechanical allodynia and thermal hyperalgesia in both hindlimbs in a dose related reduction (*p<0.05). In electrophysiological studies, topical treatment of 10 mM PPF onto the spinal surface attenuated the neuronal hyperexcitability in response to mechanical stimuli. In immunohistochemical studies, astrocytes and microglia in rats with spinal hemisection showed significantly increased GFAP and OX-42 expression in both superficial and deep dorsal horns in the lumbar spinal dorsal horn compared to sham controls (*p<0.05) that was prevented in a dose related manner by PPF. In conclusion, our present data support astrocytic and microglial activation that contributes to below-level central neuropathic pain following spinal cord injury.
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影响因子：
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