Department of Neuroscience, Physiology and Pharmacology, University College of London, Gower Street, London WC1E6BT, UK.
Mol Pain. 2009 Dec 10;5:70. doi: 10.1186/1744-8069-5-70.
Neuropathic pain is an apparently spontaneous experience triggered by abnormal physiology of the peripheral or central nervous system, which evolves with time. Neuropathic pain arising from peripheral nerve injury is characterized by a combination of spontaneous pain, hyperalgesia and allodynia. There is no evidence of this type of pain in human infants or rat pups; brachial plexus avulsion, which causes intense neuropathic pain in adults, is not painful when the injury is sustained at birth. Since infants are capable of nociception from before birth and display both acute and chronic inflammatory pain behaviour from an early neonatal age, it appears that the mechanisms underlying neuropathic pain are differentially regulated over a prolonged postnatal period.
We have performed a microarray analysis of the rat L4/L5 dorsal root ganglia (DRG), 7 days post spared nerve injury, a model of neuropathic pain. Genes that are regulated in adult rats displaying neuropathic behaviour were compared to those regulated in young rats (10 days old) that did not show the same neuropathic behaviour. The results show a set of genes, differentially regulated in the adult DRG, that are principally involved in immune system modulation. A functional consequence of this different immune response to injury is that resident macrophages cluster around the large A sensory neuron bodies in the adult DRG seven days post injury, whereas the macrophages in young DRG remain scattered evenly throughout the ganglion, as in controls.
The results show, for the first time, a major difference in the neuroimmune response to nerve injury in the dorsal root ganglion of young and adult rats. Differential analysis reveals a new set of immune related genes in the ganglia, that are differentially regulated in adult neuropathic pain, and that are consistent with the selective activation of macrophages around adult, but not young large A sensory neurons post injury. These differences may contribute to the reduced incidence of neuropathic pain in infants.
神经病理性疼痛是一种由外周或中枢神经系统异常生理引起的自发性疼痛，随着时间的推移而发展。外周神经损伤引起的神经病理性疼痛的特征是自发性疼痛、痛觉过敏和感觉异常的结合。在人类婴儿或幼鼠中没有这种类型的疼痛的证据；臂丛神经撕脱伤在成人中引起强烈的神经病理性疼痛，但在出生时受伤时并不疼痛。由于婴儿在出生前就有痛觉，并且从新生儿早期开始就表现出急性和慢性炎症性疼痛行为，因此似乎神经病理性疼痛的机制在较长的产后期间受到不同的调节。
我们对 spared nerve injury 后 7 天的大鼠 L4/L5 背根神经节 (DRG) 进行了微阵列分析，这是一种神经病理性疼痛模型。将在表现出神经病理性行为的成年大鼠中调节的基因与未表现出相同神经病理性行为的幼鼠（10 天大）中调节的基因进行比较。结果显示，一组在成年 DRG 中差异调节的基因主要参与免疫系统的调节。这种对损伤的不同免疫反应的一个功能后果是，在成年 DRG 中，损伤后 7 天，驻留巨噬细胞聚集在大 A 感觉神经元体周围，而在幼鼠 DRG 中，巨噬细胞仍均匀地分布在整个神经节中，与对照相同。
这些结果首次显示了幼鼠和成年大鼠背根神经节对神经损伤的神经免疫反应存在重大差异。差异分析揭示了一组新的与免疫相关的基因在神经节中，这些基因在成年神经病理性疼痛中差异调节，与成年但不是幼鼠大 A 感觉神经元损伤后巨噬细胞的选择性激活一致。这些差异可能有助于降低婴儿神经病理性疼痛的发生率。
