Casals-Díaz Laura, Vivó Meritxell, Navarro Xavier
Department of Cell Biology, Group of Neuroplasticity and Regeneration, Institute of Neurosciences, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Exp Neurol. 2009 May;217(1):84-95. doi: 10.1016/j.expneurol.2009.01.014. Epub 2009 Feb 3.
Peripheral nerve injuries induce plastic changes on primary afferent fibers and on the spinal circuitry, which are related to the emergence of neuropathic pain. In this study we compared three models of sciatic nerve injury in the rat with different degrees of damage and impact on regeneration capability: crush nerve injury, chronic constriction injury (CCI) and spared nerve injury (SNI). All three models were characterized by means of nerve histology, in order to describe the degenerative and regenerative process of injured axons. Nociceptive responses were evaluated by mechanical and thermal algesimetry tests. Crush animals displayed higher withdrawal thresholds on the ipsilateral paw compared to the contralateral during the time of denervation, while CCI and SNI animals showed mechanical and thermal hyperalgesia. Central plasticity was evaluated by immunohistochemical labeling of non-peptidergic (IB4-positive) and peptidergic (substance P-positive) nociceptive C-fibers on L4-L6 spinal cord sections. After crush nerve injury and SNI, we observed progressive and sustained reduction of IB4 and SP immunolabeling at the sciatic projection territory in the superficial laminae of the dorsal horn, which affected only the tibial and peroneal nerves projection areas in the case of SNI. After CCI, changes on SP-immunoreactivity were not observed, and IB4-immunoreactive area decreased initially but recovered to normal levels on the second week post-injury. Thus, nociceptive responses depend on the type of injury, and the immunoreactivity pattern of afferent fibers at the spinal cord display changes less pronounced after partial than complete sciatic nerve injury. Although signs of neuropathic pain appear in all three lesion models, nociceptive responses and central plasticity patterns differ between them.
周围神经损伤会在初级传入纤维和脊髓回路中引发可塑性变化，这与神经性疼痛的出现有关。在本研究中，我们比较了大鼠坐骨神经损伤的三种模型，它们具有不同程度的损伤以及对再生能力的影响：压迫性神经损伤、慢性压迫性损伤（CCI）和保留神经损伤（SNI）。通过神经组织学对所有三种模型进行表征，以描述受损轴突的退变和再生过程。通过机械和热痛觉测定试验评估伤害性反应。在去神经支配期间，与对侧相比，压迫组动物同侧爪的退缩阈值更高，而CCI和SNI组动物表现出机械性和热性痛觉过敏。通过对L4-L6脊髓节段的非肽能（IB4阳性）和肽能（P物质阳性）伤害性C纤维进行免疫组织化学标记来评估中枢可塑性。在压迫性神经损伤和SNI后，我们观察到背角浅层坐骨神经投射区域的IB4和SP免疫标记逐渐且持续减少，在SNI的情况下，仅影响胫神经和腓总神经的投射区域。CCI后，未观察到SP免疫反应性的变化，IB4免疫反应区域最初减少，但在损伤后第二周恢复到正常水平。因此，伤害性反应取决于损伤类型，并且与完全性坐骨神经损伤相比，部分性坐骨神经损伤后脊髓传入纤维的免疫反应模式变化不太明显。尽管在所有三种损伤模型中都出现了神经性疼痛的迹象，但它们之间的伤害性反应和中枢可塑性模式有所不同。
