Cytokine and growth factor immunohistochemical spinal profiles in two animal models of mononeuropathy

Cytokine and growth factor immunohistochemical spinal profiles in two animal models of mononeuropathy
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DOI:
10.1016/s0006-8993(97)00209-6
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发表时间:
1997-06-06
期刊:
影响因子:
2.9
通讯作者:
Rickman, AJ
Rickman, AJ
中科院分区:
医学3区
文献类型:
--
作者:
DeLeo, JA;Colburn, RW;Rickman, AJ

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神经损伤导致中枢神经免疫反应,这可能是人类慢性神经性疼痛发展和维持的组成部分。最近的数据表明,细胞因子和生长因子可能与外周和中枢神经系统部位疼痛状态的产生密切相关。我们利用免疫组织化学方法在大鼠神经性疼痛模型中研究这一现象。具体来说,我们采用了特征良好的神经病变模型,导致人类神经性疼痛的行为暗示;一种坐骨神经冻伤,称为坐骨冷冻神经松解,一种慢性收缩性坐骨神经损伤。与正常、未手术的大鼠相比,在坐骨冷冻神经溶解后3、14、35天或慢性收缩损伤后6天,我们用免疫组织化学方法检测了细胞因子、白细胞介素-1 β (IL-1 β)、肿瘤坏死因子- α (tnf - α)以及生长因子、碱性成纤维细胞生长因子(bFGF)和转化生长因子- β 1 (tgf - β)的脊柱定位。正常组腰椎组织弥漫性细胞因子/生长因子染色。然而,细胞谱定量显示,在研究的两种单神经病变模型中,腰椎IL-1 β、tnf - α和tcf - β样免疫反应性(LI)增加。在坐骨冷冻神经溶解后3天,同侧背角和腹角存在强烈的bFGF LI。第14天,对侧背侧和腹侧也观察到bFGF LI。相比之下,我们发现慢性收缩损伤后的腰椎脊髓没有明显的染色差异。该研究表明,周围神经损伤后脊髓中特异性细胞因子和生长因子样表达增加。研究还显示,在两种不同的单神经病变模型中,bFGF的表达存在差异。这些结果进一步证明,中枢细胞因子的产生可能通过神经免疫级联反应参与了神经损伤后模拟神经性疼痛行为的发展和维持。(C) 1997爱思唯尔科学有限公司
Nerve injury leads to central neuroimmunologic responses that may be integral to the development and maintenance of chronic neuropathic pain in humans, Recent data have demonstrated that cytokines and growth factors may be strongly implicated in the generation of pain states at both peripheral and central nervous system sites. We utilized immunohistochemical methods to investigate this phenomenon in rat models of neuropathic pain. Specifically, we employed well-characterized models of neuropathy that result in behaviors suggestive of neuropathic pain in humans; a freeze lesion of the sciatic nerve, termed sciatic cryoneurolysis, and a chronic constriction sciatic nerve injury. We used immunohistochemistry to examine spinal localization of the cytokines, interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and the growth factors, basic fibroblast growth factor (bFGF), and transforming growth factor-beta 1 (TGF-beta) at 3, 14, and 35 days following sciatic cryoneurolysis or 6 days following chronic constriction injury as compared with normal, unoperated rats, There was minimal, diffuse cytokine/growth factor staining in lumbar spinal tissue from the normal group. However, cell profile quantification demonstrated increases in lumbar spinal IL-1 beta, TNF-alpha- and TCF-beta-like immunoreaftivitg (LI) in both mononeuropathy models studied, At 3 days following sciatic cryoneurolysis, intense bFGF LI was present in the ipsilateral dorsal and ventral horn. By 14 days bFGF LI was also observed in contralateral dorsal and ventral hems. In contrast, we found no obvious staining differences in lumbar spinal cord following the chronic constriction injury. This study demonstrated increased specific cytokine and growth factor-like expression in the spinal cord following peripheral nerve injuries. It also showed a differential expression of bFGF in two distinct mononeuropathy models, These results provide further evidence that central cytokine production via a neuroimmune cascade may be involved in the development and maintenance of behaviors that mimic neuropathic pain following nerve injury. (C) 1997 Elsevier Science B.V.