The persistent release of HMGB1 contributes to tactile hyperalgesia in a rodent model of neuropathic pain.
The persistent release of HMGB1 contributes to tactile hyperalgesia in a rodent model of neuropathic pain.
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DOI：
10.1186/1742-2094-9-180
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发表时间：
2012-07-23
影响因子：
9.3
通讯作者：
White FA
中科院分区：
文献类型：
--
作者：
Feldman P;Due MR;Ripsch MS;Khanna R;White FA
高迁移率组盒-1蛋白（HMGB1）是一种调节全身基因表达的核蛋白。它也可以在组织损伤或损伤后成为细胞质并作为神经调节细胞因子发挥作用。HMGB1在神经损伤后影响周围神经系统的方式尚不清楚。本研究探讨了HMGB1信号在啮齿动物神经性疼痛行为维持中的作用程度。HMGB1从细胞核重新分布到细胞质中发生在胫骨神经损伤大鼠的感觉神经元和暴露于去极化刺激后的感觉神经元样细胞系中。我们还观察到外源性HMGB1给药于来自naïve或TNI啮齿动物的急性分离的感觉神经元会引起兴奋性增加。此外，全身注射甘草酸（50mg /kg; i.p.），一种已知的HMGB1抑制剂，在神经损伤后14天和3个月逆转tni诱导的机械性痛觉过敏。我们已经发现，感觉神经元持续内源性释放HMGB1可能是一种有效的、生理相关的神经元兴奋性调节剂。更重要的是，使用抗炎化合物和已知的HMGB1抑制剂甘草酸，可能通过其中和细胞因子的能力，能够减少周围神经病变模型中的持续疼痛行为。确定HMGB1作为潜在的治疗靶点可能有助于更好地理解与慢性疼痛综合征相关的机制。
High-mobility group box-1 protein (HMGB1) is a nuclear protein that regulates gene expression throughout the body. It can also become cytoplasmic and function as a neuromodulatory cytokine after tissue damage or injury. The manner in which HMGB1 influences the peripheral nervous system following nerve injury is unclear. The present study investigated the degree to which HMGB1 signaling contributes to the maintenance of neuropathic pain behavior in the rodent. Redistribution of HMGB1 from the nucleus to the cytoplasm occurred in both sensory neurons derived from a tibial nerve injured (TNI) rat and in a sensory neuron-like cell line following exposure to a depolarizing stimulus. We also observe that exogenous administration of HMGB1 to acutely dissociated sensory neurons derived from naïve or TNI rodents elicit increased excitability. Furthermore systemic injection of glycyrrhizin (50 mg/kg; i.p.), a known inhibitor of HMGB1, reversed TNI-induced mechanical hyperalgesia at fourteen days and three months following nerve injury. We have identified that a persistent endogenous release of HMGB1 by sensory neurons may be a potent, physiologically relevant modulator of neuronal excitability. More importantly, the use of the anti-inflammatory compound and known inhibitor of HMGB1, glycyrrhizin, has the ability to diminish persistent pain behavior in a model of peripheral neuropathy, presumably through its ability to neutralize the cyotkine. The identification of HMGB1 as a potential therapeutic target may contribute to a better understanding of mechanisms associated with chronic pain syndromes.
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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：
--
作者：
Mollica, Luca;De Marchis, Francesco;Bianchi, Marco E.
通讯作者：
Bianchi, Marco E.
影响因子：
11.1
作者：
Müller, S;Ronfani, L;Bianchi, ME
通讯作者：
Bianchi, ME
影响因子：
7.6
作者：
Diogenes, A.;Ferraz, C. C. R.;Hargreaves, K. M.
通讯作者：
Hargreaves, K. M.
影响因子：
82.9
作者：
Maroso, Mattia;Balosso, Silvia;Vezzani, Annamaria
通讯作者：
Vezzani, Annamaria