Localization of N-type Ca2+ channels in the rat spinal cord following chronic constrictive nerve injury
Localization of N-type Ca2+ channels in the rat spinal cord following chronic constrictive nerve injury
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DOI：
10.1007/s00221-002-1217-3
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发表时间：
2002-12-01
影响因子：
2
通讯作者：
Yaksh, TL
中科院分区：
文献类型：
--
作者：
Cizkova, D;Marsala, J;Yaksh, TL
以往的研究表明，脊髓L型、N型和P型钙通道阻滞剂对神经损伤所致的疼痛行为具有有效的调节作用。在本工作中，我们利用坐骨神经松弛结扎模型，研究了神经结扎后触觉和冷觉超敏出现的时间进程以及相应的N型钙通道α(1B)亚单位在脊髓中的表达。在结扎后1周内，大多数大鼠对机械刺激(von Frey细丝)产生单侧敏感性，并对冷敏感，并持续30天。对假手术动物脊髓的α(1B)亚单位的免疫细胞化学分析显示，在浅层1-11以及腹侧的α运动神经元中有一种光滑、中等的染色模式。在结扎神经的动物中，从结扎神经后5-20天，在同侧背角观察到强烈的点状免疫反应。最显著的α(1B)亚单位上调出现在椎板II(IIO、III)的内侧和外侧，从L4和L5脊髓节段的内侧向外侧延伸。慢性压迫性损伤后的行为改变与相应脊髓节段α(1B)亚单位的上调直接相关。这些数据表明，脊髓α(1B)亚单位的上调可能在周围神经损伤后疼痛状态的启动和维持中发挥重要作用。
Previous studies have shown that spinal L-type, N-type, and P-type Ca2+-channel blockers are effective in modulating pain behavior caused nerve injury. In the present work, using the loose ligation of the sciatic nerve model, we characterized the time course of the appearance of tactile and cold allodynia and the corresponding spinal expression of the N-type Ca2+ channel alpha(1B)-subunit after nerve ligation. Within I week after ligation, the majority of rats developed a unilateral sensitivity to mechanical stimulation (von Frey filaments), as well as sensitivity to cold, which persisted for 30 days. Immunocytochemical analysis of the spinal cord in sham-operated animals for the alpha(1B)-subunit showed a smooth, moderate staining pattern in the superficial laminae 1-11, as well as in ventral alpha-motoneurons. In nerve-ligated animals, an intense, dot-like immunoreactivity in the ipsilateral dorsal horn was observed from 5-20 days after nerve ligation. The most prominent alpha(1B)-subunit upregulation was found in the outer as well as the inner part of lamina II (IIo, IIi), extending from the medial toward the lateral region of the L4 and L5 spinal segments. The behavioral changes which developed after chronic constriction injury directly correlated with the alpha(1B)-subunit upregulation in the corresponding spinal cord segments. These data suggest that upregulation of the spinal alpha(1B)-subunit may play an important role in the initiation and maintenance of pain state after peripheral nerve injury.