Baik Eunjoo, Chung Jin Mo, Chung Kyungsoon
Marine Biomedical Institute and the Department of Anatomy and Neurosciences, University of Texas Medical Branch, Galveston, Texas 77555, USA.
J Pain. 2003 May;4(4):212-21. doi: 10.1016/s1526-5900(03)00617-5.
Inflammation of a peripheral nerve (neuritis) causes mechanical and thermal hyperalgesia in the region in which the inflamed nerve innervates. We investigated whether peripherally applied norepinephrine (NE) would exacerbate mechanical hyperalgesia in rats with neuritis. After inflammation of the left L5 spinal nerve with complete Freund's adjuvant, the foot withdrawal thresholds to mechanical stimuli applied to the affected hind paw (mechanical thresholds) were decreased significantly, indicating the development of mechanical hyperalgesia. An intradermal injection of NE to the affected paw further aggravated mechanical hyperalgesia transiently (1-3 days) and then recovered to the pre-NE injection levels afterwards. This responsiveness to NE (adrenergic sensitivity) was observed not only while rats were showing inflammatory hyperalgesia but also after recovering from it. The effect of NE on mechanical hyperalgesia was mediated by both peripheral alpha(1)- and alpha(2)-adrenoceptors. Immunohistochemical study of the previously inflamed nerve showed that proinflammatory cytokine tumor necrosis factor immunoreactivity was significantly higher in the rats showing adrenergic sensitivity compared to rats without adrenergic sensitivity. The data thus suggest that peripheral NE, when released in an excessive amount from the sympathetic nervous system, might play an important role in the aggravation of pain in neuritis.
外周神经炎症（神经炎）会导致炎症神经所支配区域出现机械性和热性痛觉过敏。我们研究了外周应用去甲肾上腺素（NE）是否会加重神经炎大鼠的机械性痛觉过敏。用完全弗氏佐剂使左侧L5脊神经发生炎症后，对施加于患侧后爪的机械刺激的足趾退缩阈值（机械阈值）显著降低，表明出现了机械性痛觉过敏。向患侧爪皮内注射NE会使机械性痛觉过敏短暂加剧（1 - 3天），之后恢复到注射NE前的水平。不仅在大鼠表现出炎性痛觉过敏时，而且在从炎性痛觉过敏恢复后，均观察到对NE的这种反应性（肾上腺素能敏感性）。NE对机械性痛觉过敏的作用由外周α(1)-和α(2)-肾上腺素能受体介导。对先前发炎神经的免疫组织化学研究表明，与无肾上腺素能敏感性的大鼠相比，表现出肾上腺素能敏感性的大鼠中促炎细胞因子肿瘤坏死因子的免疫反应性显著更高。因此，数据表明，当外周NE从交感神经系统过量释放时，可能在神经炎疼痛加重中起重要作用。
