Interleukin-1β overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents.
Interleukin-1β overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents.
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DOI：
10.1177/1744806916646784
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发表时间：
2016
期刊：
影响因子：
3.3
通讯作者：
Liu XG
中科院分区：
文献类型：
--
作者：
Gui WS;Wei X;Mai CL;Murugan M;Wu LJ;Xin WJ;Zhou LJ;Liu XG
慢性疼痛通常伴有短期记忆缺陷和抑郁症。目前，人们认为短期记忆缺陷和抑郁症是慢性疼痛的后果。在这里，我们测试的假设，症状可能是由白细胞介素-1 β（IL-1β）在受损的神经独立于神经病理性疼痛后，备用神经损伤大鼠和小鼠的过度生产。机械性异常性疼痛是神经病理性疼痛的一个行为学标志，在保留神经损伤大鼠中，机械性异常性疼痛与短期记忆障碍和抑郁行为无关。坐骨神经损伤后，IL-1β在损伤的坐骨神经、血浆以及与疼痛、记忆和情绪密切相关的中枢神经系统区域（包括脊髓背角、海马、前额叶皮质、丘脑核和杏仁核）中表达上调。重要的是，通过在大鼠中坐骨周施用IL-1β中和抗体或在小鼠中缺失IL-1受体1型，基本上预防了备用神经损伤诱导的记忆缺陷、抑郁和疼痛行为。此外，通过重复静脉注射重组大鼠IL-1β（rrIL-1β），以确定从备用神经损伤大鼠的病理浓度，在幼稚大鼠中模拟备用神经损伤诱导的行为异常。此外，小胶质细胞被备用神经损伤和静脉注射rrIL-1β激活，并且备用神经损伤的作用被坐骨周施用抗IL-1β基本上逆转。神经病理性疼痛不是认知和情绪障碍发展的必要条件，而外周神经损伤后损伤坐骨神经中IL-1β的过度产生可能是神经病理性疼痛、记忆缺陷和抑郁产生的共同机制。
Chronic pain is often accompanied by short-term memory deficit and depression. Currently, it is believed that short-term memory deficit and depression are consequences of chronic pain. Here, we test the hypothesis that the symptoms might be caused by overproduction of interleukin-1beta (IL-1β) in the injured nerve independent of neuropathic pain following spared nerve injury in rats and mice. Mechanical allodynia, a behavioral sign of neuropathic pain, was not correlated with short-term memory deficit and depressive behavior in spared nerve injury rats. Spared nerve injury upregulated IL-1β in the injured sciatic nerve, plasma, and the regions in central nervous system closely associated with pain, memory and emotion, including spinal dorsal horn, hippocampus, prefrontal cortex, nucleus accumbens, and amygdala. Importantly, the spared nerve injury-induced memory deficits, depressive, and pain behaviors were substantially prevented by peri-sciatic administration of IL-1β neutralizing antibody in rats or deletion of IL-1 receptor type 1 in mice. Furthermore, the behavioral abnormalities induced by spared nerve injury were mimicked in naïve rats by repetitive intravenous injection of re combinant rat IL-1β (rrIL-1β) at a pathological concentration as determined from spared nerve injury rats. In addition, microglia were activated by both spared nerve injury and intravenous injection of rrIL-1β and the effect of spared nerve injury was substantially reversed by peri-sciatic administration of anti-IL-1β. Neuropathic pain was not necessary for the development of cognitive and emotional disorders, while the overproduction of IL-1β in the injured sciatic nerve following peripheral nerve injury may be a common mechanism underlying the generation of neuropathic pain, memory deficit, and depression.