Neuropathic pain in rats with a partial sciatic nerve ligation is alleviated by intravenous injection of monoclonal antibody to high mobility group box-1.
Neuropathic pain in rats with a partial sciatic nerve ligation is alleviated by intravenous injection of monoclonal antibody to high mobility group box-1.
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DOI：
10.1371/journal.pone.0073640
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Nakata Y
中科院分区：
文献类型：
--
作者：
Nakamura Y;Morioka N;Abe H;Zhang FF;Hisaoka-Nakashima K;Liu K;Nishibori M;Nakata Y
高迁移率族蛋白1（HMGB 1）与炎症性疾病的发病机制有关。先前的研究报道，静脉注射抗HMGB 1单克隆抗体显著减轻中风大鼠模型的脑水肿，可能是通过减弱胶质细胞活化。周围神经损伤导致脊髓后角胶质细胞活性增加。因此，抗HMGB 1抗体也可能有效减轻外周神经损伤诱导的疼痛。在部分坐骨神经结扎（PSNL）后，用抗HMGB 1或对照IgG处理大鼠。静脉注射抗HMGB 1单克隆抗体（2 mg/kg）显着改善PSNL诱导的后爪触觉超敏反应在7，14和21天，但不是3天，结扎后，而对照IgG对触觉超敏反应没有影响。PSNL后7、14和21天脊髓背角HMGB 1蛋白表达显著增加;抗HMGB 1抗体的疗效可能与HMGB 1蛋白的存在有关。此外，损伤诱导的HMGB 1从细胞核到胞质溶胶的易位主要发生在背角神经元中，而不是在星形胶质细胞和小胶质细胞中，表明HMGB 1的神经元来源。PSNL后21天，与假手术侧相比，同侧背角侧的星形胶质细胞（胶质细胞酸性蛋白（GFAP））、小胶质细胞（离子钙结合适配分子1（Iba 1））和脊髓神经元（cFos）活性标志物显著增加。抗HMGB 1单克隆抗体治疗可显著降低损伤诱导的cFos和Iba 1表达，但对GFAP无影响。结果表明，神经损伤引起HMGB 1从脊髓神经元的合成和释放，促进小胶质细胞和神经元的活动，这反过来又导致神经病理性疼痛的症状。因此，靶向HMGB 1可能是治疗慢性疼痛的一种有用的治疗策略。
High mobility group box-1 (HMGB1) is associated with the pathogenesis of inflammatory diseases. A previous study reported that intravenous injection of anti-HMGB1 monoclonal antibody significantly attenuated brain edema in a rat model of stroke, possibly by attenuating glial activation. Peripheral nerve injury leads to increased activity of glia in the spinal cord dorsal horn. Thus, it is possible that the anti-HMGB1 antibody could also be efficacious in attenuating peripheral nerve injury-induced pain. Following partial sciatic nerve ligation (PSNL), rats were treated with either anti-HMGB1 or control IgG. Intravenous treatment with anti-HMGB1 monoclonal antibody (2 mg/kg) significantly ameliorated PSNL-induced hind paw tactile hypersensitivity at 7, 14 and 21 days, but not 3 days, after ligation, whereas control IgG had no effect on tactile hypersensitivity. The expression of HMGB1 protein in the spinal dorsal horn was significantly increased 7, 14 and 21 days after PSNL; the efficacy of the anti-HMGB1 antibody is likely related to the presence of HMGB1 protein. Also, the injury-induced translocation of HMGB1 from the nucleus to the cytosol occurred mainly in dorsal horn neurons and not in astrocytes and microglia, indicating a neuronal source of HMGB1. Markers of astrocyte (glial fibrillary acidic protein (GFAP)), microglia (ionized calcium binding adaptor molecule 1 (Iba1)) and spinal neuron (cFos) activity were greatly increased in the ipsilateral dorsal horn side compared to the sham-operated side 21 days after PSNL. Anti-HMGB1 monoclonal antibody treatment significantly decreased the injury-induced expression of cFos and Iba1, but not GFAP. The results demonstrate that nerve injury evokes the synthesis and release of HMGB1 from spinal neurons, facilitating the activity of both microglia and neurons, which in turn leads to symptoms of neuropathic pain. Thus, the targeting of HMGB1 could be a useful therapeutic strategy in the treatment of chronic pain.
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HMGB1：内源性危险信号。
影响因子：
5.7
作者：
Klune, John R.;Dhupar, Rajeev;Cardinal, Jon;Billiar, Timothy R.;Tsung, Allan
通讯作者：
Tsung, Allan
影响因子：
6
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影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
7.4
作者：
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通讯作者：
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