Christensen M D, Hulsebosch C E
Marine Biomedical Institute, University of Texas Medical Branch, Galveston 77555-1069, USA.
Exp Neurol. 1997 Oct;147(2):463-75. doi: 10.1006/exnr.1997.6608.
Spinal cord injury (SCI) results in chronic pain states in which the underlying mechanism is poorly understood. To begin to explore possible mechanisms, calcitonin gene-related peptide (CGRP), a neuropeptide confined to fine primary afferent terminals in laminae I and II in the dorsal horn of the spinal cord and implicated in pain transmission, was selected. Immunocytochemical techniques were used to examine the temporal and spatial distribution of CGRP in the spinal cord following T-13 spinal cord hemisection in adult male Sprague-Dawley rats compared to that seen in sham controls. Spinal cords from both hemisected and sham control groups (N = 5, per time point) were examined on postoperative day (POD) 3, 5, 7, 14, and 108 following surgery. Sham operated rats displayed CGRP immunoreaction product in laminae I and II outer, Lissauer's tract, dorsal roots, and motor neurons of the ventral horn. In the hemisected group, densiometric data demonstrated an increased deposition of reaction product that was statistically significant, in laminae III and IV, both ipsilateral and contralateral to the lesion that extended at least two segments rostral and caudal to the hemisection site by POD 14, and remained significantly elevated as long as POD 108. Since upregulation alone of CGRP would occur in an acute temporal window (by 2 to 3 days following spinal injury), these results are interpreted to be invasion of laminae III and IV by sprouting of CGRP containing fine primary afferents. Intrathecal delivery of antibodies against purified 2.5S nerve growth factor for 14 days to the hemisected group resulted in CGRP density in laminae I through IV that was significantly less than that seen in untreated or vehicle treated hemisected groups and to sham controls. These data indicate changes in density and distribution of CGRP following spinal hemisection that can be manipulated by changes in endogenous levels of NGF. These observations suggest possible strategies for intervention in the development of various pain states in human SCI.
脊髓损伤（SCI）会导致慢性疼痛状态，但其潜在机制尚不清楚。为了开始探索可能的机制，我们选择了降钙素基因相关肽（CGRP），这是一种局限于脊髓背角I层和II层中细小初级传入终末的神经肽，与疼痛传递有关。我们采用免疫细胞化学技术，研究成年雄性Sprague-Dawley大鼠T-13脊髓半切术后脊髓中CGRP的时空分布，并与假手术对照组进行比较。在术后第3、5、7、14和108天检查半切组和假手术对照组（每个时间点N = 5）的脊髓。假手术大鼠在I层和II层外侧、Lissauer束、背根和腹角运动神经元中显示出CGRP免疫反应产物。在半切组中，光密度数据显示反应产物的沉积增加，具有统计学意义，在损伤同侧和对侧的III层和IV层中，到术后第14天，该沉积至少在半切部位的头侧和尾侧延伸两个节段，并且直到术后第108天仍显著升高。由于CGRP的上调仅会在急性时间窗内（脊髓损伤后2至3天）发生，因此这些结果被解释为含有CGRP的细小初级传入纤维发芽侵入III层和IV层。向半切组鞘内注射抗纯化2.5S神经生长因子的抗体14天，导致I层至IV层的CGRP密度显著低于未治疗或用载体治疗的半切组以及假手术对照组。这些数据表明脊髓半切术后CGRP的密度和分布发生了变化，这些变化可通过内源性神经生长因子水平的改变来调控。这些观察结果提示了干预人类脊髓损伤中各种疼痛状态发展的可能策略。
