Spinal astrocyte gap junctions contribute to oxaliplatin-induced mechanical hypersensitivity.
Spinal astrocyte gap junctions contribute to oxaliplatin-induced mechanical hypersensitivity.
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DOI：
10.1016/j.jpain.2012.11.002
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发表时间：
2013-02
期刊：
影响因子：
4
通讯作者：
Dougherty, Patrick M.
中科院分区：
文献类型：
--
作者：
Yoon, Seo-Yeon;Robinson, Caleb R.;Zhang, Haijun;Dougherty, Patrick M.
脊髓神经胶质细胞参与了多种类型的炎症性和神经性疼痛的发生。在这里，我们探讨了脊髓星形胶质细胞和星形胶质细胞缝隙连接在奥沙利铂诱导的机械超敏反应中的作用。奥沙利铂治疗后脊髓背角胶质纤维酸性蛋白(GFAP)的表达在第7天显著增加，第14天恢复正常，提示化疗对脊髓星形胶质细胞有一过性激活作用。在化疗后第7天和第14天，星形胶质细胞特异性缝隙连接蛋白Cx43在背角均显着增加，而神经元(Cx36)和少突胶质细胞(Cx32)缝隙连接蛋白无明显变化。用甘草甜素阻断星形胶质细胞缝隙连接可剂量依赖性地阻止奥沙利铂诱导的机械超敏反应和脊髓GFAP表达的增加，但一旦奥沙利铂诱导的机械超敏反应完全发展，则无作用。这些结果提示，奥沙利铂化疗可诱导脊髓星形胶质细胞的激活，并伴随着星形胶质细胞-星形胶质细胞缝隙连接通过连接蛋白43的表达增加。脊髓星形胶质细胞的这些改变似乎有助于诱导而不是维持奥沙利铂诱导的机械超敏反应。综合这些结果，提示靶向脊髓星形胶质细胞/星形胶质细胞特异性缝隙连接可能是预防奥沙利铂诱导的神经病变的一种新的治疗策略。
Spinal glial cells contribute to the development of many types of inflammatory and neuropathic pain. Here the contribution of spinal astrocytes and astrocyte gap junctions to oxaliplatin-induced mechanical hypersensitivity was explored. The expression of glial fibrillary acidic protein (GFAP) in spinal dorsal horn was significantly increased at day 7 but recovered at day 14 after oxaliplatin treatment, suggesting a transient activation of spinal astrocytes by chemotherapy. Astrocyte-specific gap junction protein connexin 43 was significantly increased in dorsal horn at both day 7 and day 14 following chemotherapy but neuronal (connexin 36) and oligodendrocyte (connexin 32) gap junction proteins did not show any change. Blockade of astrocyte gap junction with carbenoxolone prevented oxaliplatin-induced mechanical hypersensitivity in a dose-dependent manner and the increase of spinal GFAP expression, but had no effect once the mechanical hypersensitivity induced by oxaliplatin had fully developed. These results suggest that oxaliplatin chemotherapy induces the activation of spinal astrocytes and this is accompanied by increased expression of astrocyte-astrocyte gap junction connections via connexin 43. These alterations in spinal astrocytes appear to contribute to the induction but not the maintenance of oxaliplatin-induced mechanical hypersensitivity. Combined these results suggest that targeting spinal astrocyte/astrocyte-specific gap junction could be a new therapeutic strategy to prevent oxaliplatin-induced neuropathy.
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DOI：
10.1097/spc.0b013e328342f9cc
发表时间：
2011-03-01
影响因子：
2.1
作者：
Farquhar-Smith, Paul
通讯作者：
Farquhar-Smith, Paul
影响因子：
7.4
作者：
Carlton SM;Du J;Tan HY;Nesic O;Hargett GL;Bopp AC;Yamani A;Lin Q;Willis WD;Hulsebosch CE
通讯作者：
Hulsebosch CE
影响因子：
2.9
作者：
Cata, Juan P.;Weng, Han-Rong;Dougherty, Patrick M.
通讯作者：
Dougherty, Patrick M.
影响因子：
8.4
作者：
Binder, Andreas;Stengel, Maike;Baron, Ralf
通讯作者：
Baron, Ralf
影响因子：
1.7
作者：
Chiang, Chen Yu;Li, Zhaohui;Sessle, Barry J.
通讯作者：
Sessle, Barry J.