Induction of high mobility group box-1 in dorsal root ganglion contributes to pain hypersensitivity after peripheral nerve injury
Induction of high mobility group box-1 in dorsal root ganglion contributes to pain hypersensitivity after peripheral nerve injury
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DOI：
10.1016/j.pain.2010.03.023
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发表时间：
2010-06-01
期刊：
影响因子：
7.4
通讯作者：
Amaya, Fumimasa
中科院分区：
文献类型：
--
作者：
Shibasaki, Masayuki;Sasaki, Mika;Amaya, Fumimasa
促炎症细胞因子高迁移率族蛋白-1(HMGB-1)参与中枢神经系统的炎症反应，但对其在外周神经系统的生物学作用知之甚少。本研究从周围神经损伤所致疼痛超敏的病理生理学角度探讨了HMGB-1在初级传入神经中的作用。实时荧光定量聚合酶链式反应证实，脊神经结扎后1d，HMGB-1mRNA在背根节(DRG)和脊神经中表达增加。损伤的L5和未损伤的L4均可观察到HMGB-1mRNA的表达。HMGB-1的免疫组织化学结果显示，SNL诱导的HMGB-1在DRG的初级传入神经元和卫星胶质细胞(SGCs)以及脊神经的Schwann细胞中均有表达。HMGB-1的上调与其信号从胞核到胞浆的移位有关。将HMGB-1注射到坐骨神经可引起一过性行为痛敏。抗HMGB-1的中和抗体成功地缓解了SNL治疗后的机械性超敏反应。晚期糖基化终产物受体(RAGE)是HMGB-1的主要受体之一，表达于DRG的初级传入神经元和SGCs，也表达于脊神经的雪旺细胞。这些结果表明，HMGB-1被合成并分泌到背根节和脊神经，参与了神经损伤后神经病理性疼痛的发生。因此，阻断HMGB-1/RAGE信号通路可能是治疗神经病理性疼痛的一种有前途的治疗策略。(C)2010年国际疼痛研究协会。爱思唯尔出版公司版权所有。
Pro-inflammatory cytokine high mobility group box-1 (HMGB-1) is involved in inflammation in the central nervous system, but less is known about its biological effects in the peripheral nervous system. In the present study, the role of HMGB-1 in the primary afferent nerve was investigated in the context of the pathophysiology of peripheral nerve injury-induced pain hypersensitivity. Real-time PCR confirmed an increase in HMGB-1 mRNA expression in the dorsal root ganglion (DRG) and spinal nerve at 1 day after spinal nerve ligation (SNL). Induction of HMGB-1 mRNA was observed in both injured L5 and uninjured L4. Immunohistochemistry for HMGB-1 revealed that SNL-induced HMGB-1 expression in the primary afferent neurons and satellite glial cells (SGCs) in the DRG, and in Schwann cells in the spinal nerve. Up-regulation of HMGB-1 was associated with translocation of its signal from the nucleus to the cytoplasm. Injection of HMGB-1 into the sciatic nerve produces transient behavioural hyperalgesia. Neutralizing antibody against HMGB-1 successfully alleviated the mechanical allodynia observed after SNL treatment. Receptor for advanced glycation end products (RAGE), one of the major receptors for HMGB-1, was expressed in the primary afferent neurons and SGCs in the DRG, as well as in Schwann cells in the spinal nerve. These results indicate that HMGB-1 is synthesized and secreted into the DRG and spinal nerve, and contributes to the development of neuropathic pain after nerve injury. Blocking HMGB-1/RAGE signalling might thus be a promising therapeutic strategy for the management of neuropathic pain. (C) 2010 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.