Increase of interleukin-6 mRNA in the spinal cord following peripheral nerve injury in the rat: potential role of IL-6 in neuropathic pain
Increase of interleukin-6 mRNA in the spinal cord following peripheral nerve injury in the rat: potential role of IL-6 in neuropathic pain
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DOI：
10.1016/s0169-328x(98)00257-5
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发表时间：
1998-11-20
期刊：
影响因子：
--
通讯作者：
DeLeo, JA
中科院分区：
文献类型：
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作者：
Arruda, JL;Colburn, RW;DeLeo, JA
白介素6(IL-6)是一种多功能细胞因子，其作用包括调节造血祖细胞和其他细胞系的增殖、分化和成熟；调节某些肿瘤细胞的生长；控制细胞的代谢活动。最初从免疫系统和炎症的角度对其进行描述，越来越多的证据支持IL-6在外周和中枢神经系统神经元的发育、分化、再生和退化中发挥重要作用。我们先前已经证明，在周围神经损伤导致大鼠神经病理性疼痛行为的反应中，脊髓中免疫反应样IL-6蛋白显著升高。在目前的研究中，我们的目标是通过测量与神经病理性疼痛相关的单神经病手术后脊髓IL-6mRNA表达的任何可检测到的增加来确定IL-6蛋白的来源是否来自中枢神经系统：脊髓神经冷冻神经松解术(SPCN)或脊髓神经紧密结扎术(SPTL)。应用原位杂交和地高辛标记的寡核苷酸，发现SPCN后3d、7d和SPTL后7d，脊髓背角和腹角神经元中IL-6mRNA的表达均显著升高。Neun系列染色证实，IL-6mRNA表达的细胞定位主要是神经元。例如，在SPCN 7d组，同侧背角IL-6mRNA细胞图谱与正常组相比有显著差异(38.7vs.4.89+/-1.6，p<；0.001)。这些数据显示了中枢和脊髓对周围神经损伤的促炎细胞因子的产生。此外，这些结果增加了越来越多的文献，这些文献暗示这些免疫产物，细胞因子，作为潜在的神经调节器/神经递质，并为它们在导致慢性疼痛的伤害性处理中的作用提供了进一步的证据。(C)1998 Elsevier Science B.V.保留所有权利。
Interleukin-6 (IL-6) is a multifunctional cytokine whose actions include modulation of proliferation, differentiation, and maturation of hemapoietic progenitors and other cell lineages; growth regulation of certain carcinoma cell lines; and control of cellular metabolic activities. Initially described in terms of its activities in the immune system and inflammation, accumulating evidence supports an essential role of IL-6 in the development, differentiation, regeneration and degeneration of neurons in the peripheral and central nervous system. We have previously demonstrated that immunoreactive-like IL-6 protein is significantly elevated in the spinal cord in response to peripheral nerve injury that results in neuropathic pain behaviors in the rat. In the current study, our objective was to determine if the source of IL-6 protein was endogenous to the central nervous system by measuring any detectable increases in spinal IL-6 mRNA expression following established mononeuropathy procedures associated with neuropathic pain: spinal nerve cryoneurolysis (SPCN) or spinal nerve tight ligation (SPTL). Using in situ hybridization and a digoxigenin-labeled oligonucleotide, IL-6 mRNA in neurons was significantly elevated at 3 and 7 days post SPCN and 7 days post SPTL in both dorsal and ventral horns. The cellular localization of the IL-6 mRNA expression was predominately neuronal as confirmed by NeuN serial staining. For example, in the SPCN 7 day group, IL-6 mRNA cell profiles in the ipsilateral dorsal horn were significantly different from the normal group (38.7 +/- 12.8 vs. 4.89 +/- 1.6, p < 0.001). These data demonstrate the central, spinal production of a proinflammatory cytokine in response to a peripheral nerve injury. In addition, these results add to the growing body of literature implicating these immune products, cytokines, as potential neuromodulators/neurotransmitters and provides further evidence for their role in the nociceptive processing which leads to chronic pain. (C) 1998 Elsevier Science B.V. All rights reserved.