Arruda J L, Colburn R W, Rickman A J, Rutkowski M D, DeLeo J A
Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, HB 7125, Lebanon, NH 03756, USA.
Brain Res Mol Brain Res. 1998 Nov 20;62(2):228-35. doi: 10.1016/s0169-328x(98)00257-5.
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.
白细胞介素-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谱系的增殖、分化和成熟；调控某些癌细胞系的生长；以及控制细胞代谢活动。最初是根据其在免疫系统和炎症中的活性来描述的，越来越多的证据支持IL-6在周围和中枢神经系统神经元的发育、分化、再生和退变中起重要作用。我们之前已经证明，在大鼠中，响应导致神经性疼痛行为的外周神经损伤，脊髓中免疫反应样IL-6蛋白显著升高。在本研究中，我们的目的是通过测量与神经性疼痛相关的既定单神经病变程序（脊髓神经冷冻神经lysis术（SPCN）或脊髓神经紧密结扎术（SPTL））后脊髓IL-6 mRNA表达的任何可检测到的增加，来确定IL-6蛋白的来源是否内生于中枢神经系统。使用原位杂交和地高辛标记的寡核苷酸，在SPCN后3天和7天以及SPTL后7天，背角和腹角神经元中的IL-6 mRNA均显著升高。通过NeuN系列染色证实，IL-6 mRNA表达的细胞定位主要是神经元。例如，在SPCN 7天组中，同侧背角的IL-6 mRNA细胞分布图与正常组有显著差异（38.7±12.8对4.89±1.6，p<0.001）。这些数据表明，响应外周神经损伤，脊髓会产生促炎细胞因子。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剂/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。
