Controlled release of GDNF reduces nerve root-mediated behavioral hypersensitivity.
Controlled release of GDNF reduces nerve root-mediated behavioral hypersensitivity.
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DOI：
10.1002/jor.20710
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发表时间：
2009-01
影响因子：
2.8
通讯作者：
Winkelstein, Beth A.
中科院分区：
文献类型：
--
作者：
Hubbard, Raymond D.;Martinez, Joan J.;Burdick, Jason A.;Winkelstein, Beth A.
神经根压迫在疼痛性颈部损伤模型中产生持续的行为敏感性。本研究利用可降解的聚乙二醇水凝胶将胶质细胞源性神经营养因子（GDNF）递送至损伤的神经根。在体外释放试验中，在没有神经元存在的情况下，水凝胶在7天内递送了98%的封装的GDNF，并且在皮质神经细胞原代培养物中产生了增强的突起生长。在C7背根压迫的大鼠疼痛模型中评估损伤后立即放置在根上的GDNF水凝胶的功效。对照组包括疼痛性损伤，随后是：（1）媒介物水凝胶处理（无GDNF），（2）GDNF的推注，或（3）不处理。与三个损伤对照组相比，损伤后，通过水凝胶递送GDNF的机械性异常性疼痛（n=6/组）显着减少（p<0.03）。在任何时间点，GDNF推注治疗都没有减少异常性疼痛。GDNF受体（GFRα-1）在受影响的背根神经节的小的伤害感受神经元中减少，表明损伤后受体表达减少。在GDNF水凝胶处理后的这些神经元中，GDNF受体免疫反应性相对于GDNF推注处理和未处理的大鼠显著更高（p<0.05）。这些数据表明GDNF的可降解水凝胶递送的功效，并支持神经根介导的疼痛的这种治疗方法。
Nerve root compression produces persistent behavioral sensitivity in models of painful neck injury. This study utilized degradable poly(ethylene glycol) hydrogels to deliver glial cell line-derived neurotrophic factor (GDNF) to an injured nerve root. Hydrogels delivered ∼98% of encapsulated GDNF over 7 days in an in vitro release assay without the presence of neurons and produced enhanced outgrowth of processes in cortical neural cell primary cultures. The efficacy of a GDNF hydrogel placed on the root immediately after injury was assessed in a rat pain model of C7 dorsal root compression. Control groups included painful injury followed by: (1) vehicle hydrogel treatment (no GDNF), (2) a bolus injection of GDNF, or (3) no treatment. After injury, mechanical allodynia (n=6/group) was significantly decreased with GDNF delivered by the hydrogel compared to the three injury control groups (p<0.03). The bolus GDNF treatment did not reduce allodynia at any time point. The GDNF receptor (GFRα-1) decreased in small, nociceptive neurons of the affected dorsal root ganglion, suggesting a decrease in receptor expression following injury. GDNF receptor immunoreactivity was significantly greater in these neurons following GDNF hydrogel treatment relative to GDNF bolus treated and untreated rats (p<0.05). These data suggest efficacy for degradable hydrogel delivery of GDNF and support this treatment approach for nerve root-mediated pain.
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