Abnormalities in hippocampal functioning with persistent pain.
Abnormalities in hippocampal functioning with persistent pain.
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DOI：
10.1523/jneurosci.0587-12.2012
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发表时间：
2012-04-25
期刊：
影响因子：
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通讯作者：
Apkarian AV
中科院分区：
文献类型：
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作者：
Mutso AA;Radzicki D;Baliki MN;Huang L;Banisadr G;Centeno MV;Radulovic J;Martina M;Miller RJ;Apkarian AV
慢性疼痛患者表现出焦虑、抑郁和学习记忆障碍。然而，持续的疼痛是如何影响大脑中调节这些行为的关键区域——海马体的，这方面的研究还很少。在这项研究中，我们研究了神经损伤（SNI）神经性疼痛对小鼠海马依赖行为和潜在的细胞和分子变化的影响。同时，我们测量了三组慢性疼痛患者的海马体积。我们发现SNI动物无法消除情境恐惧，并表现出更多的焦虑样行为。此外，与假手术小鼠相比，SNI小鼠表现出海马1)细胞外信号调节激酶（ERK）表达和磷酸化减少，2)神经发生减少，3)短期突触可塑性改变。为了将观察到的海马异常与人类慢性疼痛联系起来，我们测量了慢性背痛（CBP）、复杂区域疼痛综合征（CRPS）和骨关节炎（OA）患者的海马体积。与对照组相比，CBP和CRPS组的双侧海马体积明显减少，而OA组没有。这些结果表明，海马介导的行为、突触可塑性和神经发生在神经性病变啮齿动物中是异常的。这些变化可能与我们在慢性疼痛患者中看到的海马体积减少有关，这些异常可能是在这些患者中常见的学习和情绪缺陷的基础。
Chronic pain patients exhibit increased anxiety, depression, and deficits in learning and memory. Yet how persistent pain affects the key brain area regulating these behaviors, the hippocampus, has remained minimally explored. In this study we investigated the impact of spared nerve injury (SNI) neuropathic pain in mice on hippocampal-dependent behavior and underlying cellular and molecular changes. In parallel, we measured the hippocampal volume of three groups of chronic pain patients. We found that SNI animals were unable to extinguish to contextual fear and showed increased anxiety-like behavior. Additionally, SNI mice in comparison to sham animals exhibited hippocampal 1) reduced extracellular signal-regulated kinase (ERK) expression and phosphorylation, 2) decreased neurogenesis and 3) altered short-term synaptic plasticity. In order to relate the observed hippocampal abnormalities with human chronic pain, we measured the volume of human hippocampus in chronic back pain (CBP), complex regional pain syndrome (CRPS), and osteoarthritis patients (OA). Compared to controls, CBP and CRPS, but not OA, had significantly less bilateral hippocampal volume. These results indicate that hippocampus-mediated behavior, synaptic plasticity and neurogenesis are abnormal in neuropathic rodents. The changes may be related to the reduction in hippocampal volume we see in chronic pain patients, and these abnormalities may underlie learning and emotional deficits commonly observed in such patients.