DeLeo J A, Colburn R W, Rickman A J
Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA.
Brain Res. 1997 Jun 6;759(1):50-7. doi: 10.1016/s0006-8993(97)00209-6.
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-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and the growth factors, basic fibroblast growth factor (bFGF), and transforming growth factor-beta1 (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-1beta-, TNF-alpha- and TGF-beta-like immunoreactivity (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 horns. 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.
神经损伤会引发中枢神经免疫反应，这可能是人类慢性神经性疼痛发生和维持的重要因素。最近的数据表明，细胞因子和生长因子可能在周围神经系统和中枢神经系统部位疼痛状态的产生中发挥重要作用。我们利用免疫组织化学方法在神经性疼痛大鼠模型中研究这一现象。具体而言，我们采用了特征明确的神经病变模型，这些模型会导致出现类似于人类神经性疼痛的行为；坐骨神经冷冻损伤，即坐骨神经冷冻神经lysis，以及坐骨神经慢性缩窄损伤。我们使用免疫组织化学方法，在坐骨神经冷冻神经lysis后3天、14天和35天，或慢性缩窄损伤后6天，与正常未手术的大鼠相比，检测细胞因子白细胞介素-1β（IL-1β）、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-β1（TGF-β）在脊髓中的定位。正常组腰椎脊髓组织中细胞因子/生长因子染色极少且呈弥漫性。然而，细胞轮廓定量分析表明，在所研究的两种单神经病变模型中，腰椎脊髓中IL-1β、TNF-α和TGF-β样免疫反应性（LI）均增加。坐骨神经冷冻神经lysis后3天，同侧背角和腹角出现强烈的bFGF LI。到14天时，在对侧背角和腹角也观察到bFGF LI。相比之下，我们发现慢性缩窄损伤后腰椎脊髓中没有明显的染色差异。这项研究表明，周围神经损伤后脊髓中特定细胞因子和生长因子样表达增加。它还显示了bFGF在两种不同单神经病变模型中的差异表达。这些结果进一步证明，通过神经免疫级联反应产生的中枢细胞因子可能参与了神经损伤后模拟神经性疼痛行为的发生和维持。
