Role of macrophages and activated microglia in neuropathic pain associated with chronic progressive spinal cord compression
Role of macrophages and activated microglia in neuropathic pain associated with chronic progressive spinal cord compression
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DOI：
10.1038/s41598-019-52234-1
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发表时间：
2019-10-30
影响因子：
4.6
通讯作者：
Matsumine, Akihiko
中科院分区：
文献类型：
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作者：
Takeura, Naoto;Nakajima, Hideaki;Matsumine, Akihiko
神经性疼痛 (NeP) 常见于患有脊髓损伤相关疾病（例如脊髓损伤 (SCI) 和压迫性脊髓病）的患者。最近的研究描述了 SCI 中持续的胶质细胞激活和神经元过度活跃，但脊髓慢性受压中 NeP 的病理机制仍然难以捉摸。本研究的目的是确定小胶质细胞和浸润巨噬细胞在 NeP 中的作用。该研究是在嵌合脊柱骨质增生小鼠（ttw/ttw）中进行的，其特征是脊髓慢性进行性受压，作为人类压迫性脊髓病的合适模型。脊髓受压的严重程度与活化的小胶质细胞和血源性巨噬细胞的比例相关。脊髓受压与浸润巨噬细胞中丝裂原激活蛋白激酶（MAPK）的过度表达以及背角中可逆性血脊髓屏障（BSCB）破坏有关。我们的结果表明，长期脊髓压迫引起的慢性神经性疼痛与浸润的巨噬细胞、活化的小胶质细胞和 BSCB 的相关损伤以及这些细胞中 p-38 MAPK 和 p-ERK1/2 的过度表达有关。我们的研究结果可能有助于设计新疗法，以减轻与压迫性脊髓病相关的慢性神经性疼痛。
Neuropathic pain (NeP) is commonly encountered in patients with diseases associated with spinal cord damage (e.g., spinal cord injury (SCI) and compressive myelopathy). Recent studies described persistent glial activation and neuronal hyperactivity in SCI, but the pathomechanisms of NeP in chronic compression of the spinal cord remains elusive. The purpose of the present study was to determine the roles of microglia and infiltrating macrophages in NeP. The study was conducted in chimeric spinal hyperostotic mice (ttw/ttw), characterized by chronic progressive compression of the spinal cord as a suitable model of human compressive myelopathy. The severity of spinal cord compression correlated with proportion of activated microglia and hematogenous macrophages. Spinal cord compression was associated with overexpression of mitogen-activated protein kinases (MAPKs) in infiltrating macrophages and reversible blood-spinal cord barrier (BSCB) disruption in the dorsal horns. Our results suggested that chronic neuropathic pain in long-term spinal cord compression correlates with infiltrating macrophages, activated microglial cells and the associated damage of BSCB, together with overexpression of p-38 MAPK and p-ERK1/2 in these cells. Our findings are potentially useful for the design of new therapies to alleviate chronic neuropathic pain associated with compressive myelopathy.