Cervical spinal cord injury-induced neuropathic pain in male mice is associated with a persistent pro-inflammatory macrophage/microglial response in the superficial dorsal horn.
Cervical spinal cord injury-induced neuropathic pain in male mice is associated with a persistent pro-inflammatory macrophage/microglial response in the superficial dorsal horn.
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DOI：
10.1016/j.expneurol.2021.113757
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发表时间：
2021-09
影响因子：
5.3
通讯作者：
Lepore AC
中科院分区：
文献类型：
--
作者：
Brown EV;Falnikar A;Heinsinger N;Cheng L;Andrews CE;DeMarco M;Lepore AC
很大一部分患有创伤性脊髓损伤（SCI）的个体经历一定程度的使人衰弱的神经性疼痛（NP）。这种疼痛在大多数情况下仍然很难治愈，部分原因是对其潜在机制的不完全理解。中枢敏感化是指位于脊髓背角浅层（sDH）的痛传递神经元兴奋性的增加，在SCI诱导的NP的发生和维持中起着关键作用。驻留的小胶质细胞和外周单核细胞衍生的巨噬细胞（统称为MMΦ）参与促进SCI诱导的DH神经元过度兴奋。重要的是，这些MMΦ由可以在损伤的脊髓内施加促炎或抗炎信号的细胞群组成。时空表征这种异质性以了解SCI后MMΦ对NP的贡献至关重要。鉴于大多数SCI病例本质上是颈部的，我们使用了单侧C5/C6挫伤模型，该模型导致前爪持续的水平热痛觉过敏和机械异常性疼痛，这是NP相关行为的两种形式。本研究的目的是表征损伤尾侧的完整颈脊髓节段内的sDH MMΦ反应（即来自前爪足底表面的初级传入伤害性输入的位置）。颈椎SCI促进了sDH中与慢性NP表型一致的持续MMΦ反应。使用促炎和抗炎MMΦ的标志物，我们发现sDH内的MMΦ群体表现出显著的异质性，其在损伤后随时间推移而演变，包括促炎MMΦ的稳健和持续增加，其在后期尤其明显。C5/C6挫伤SCI也诱导了后爪的低位热痛觉过敏和机械性异常性疼痛;然而，我们没有观察到L4/L5脊髓sDH中明显的MMΦ反应，这表明发生在sDH中的不同炎性细胞机制可能涉及SCI后的高位与低位NP。总之，我们的研究结果揭示了SCI后疼痛传导部位内和疼痛传导部位之间的MMΦ异质性。这些数据还显示了显著和持续的促炎性MMΦ反应，表明可能在DH神经元过度兴奋和NP中起作用。
A significant portion of individuals living with traumatic spinal cord injury (SCI) experiences some degree of debilitating neuropathic pain (NP). This pain remains largely intractable in a majority of cases, due in part to an incomplete understanding of its underlying mechanisms. Central sensitization, an increase in excitability of pain transmission neurons located in superficial dorsal horn (sDH), plays a key role in development and maintenance of SCI-induced NP. Resident microglia and peripheral monocyte-derived macrophages (referred to collectively as MMΦ) are involved in promoting SCI-induced DH neuron hyperexcitability. Importantly, these MMΦ consist of populations of cells that can exert pro-inflammatory or anti-inflammatory signaling within injured spinal cord. It is critical to spatiotemporally characterize this heterogeneity to understand MMΦ contribution to NP after SCI. Given that a majority of SCI cases are cervical in nature, we used a model of unilateral C5/C6 contusion that results in persistent at-level thermal hyperalgesia and mechanical allodynia, two forms of NP-related behavior, in the forepaw. The aim of this study was to characterize the sDH MMΦ response within intact cervical spinal cord segments caudal to the lesion (i.e. the location of primary afferent nociceptive input from the forepaw plantar surface). Cervical SCI promoted a persistent MMΦ response in sDH that coincided with the chronic NP phenotype. Using markers of pro- and anti-inflammatory MMΦ, we found that the MMΦ population within sDH exhibited significant heterogeneity that evolved over time post-injury, including a robust and persistent increase in pro-inflammatory MMΦ that was especially pronounced at later times. C5/C6 contusion SCI also induced below-level thermal hyperalgesia and mechanical allodynia in the hindpaw; however, we did not observe a pronounced MMΦ response in sDH of L4/L5 spinal cord, suggesting that different inflammatory cell mechanisms occurring in sDH may be involved in at-level versus below-level NP following SCI. In conclusion, our findings reveal significant MMΦ heterogeneity both within and across pain transmission locations after SCI. These data also show a prominent and persistent pro-inflammatory MMΦ response, suggesting a possible role in DH neuron hyperexcitability and NP.
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影响因子：
2.7
作者：
Clark AK;Old EA;Malcangio M
通讯作者：
Malcangio M
影响因子：
2.5
作者：
Jiang, MC;Liu, L;Gebhart, GF
通讯作者：
Gebhart, GF
DOI：
10.1523/jneurosci.3992-08.2009
发表时间：
2009-03-25
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Gensel JC;Nakamura S;Guan Z;van Rooijen N;Ankeny DP;Popovich PG
通讯作者：
Popovich PG
影响因子：
7.4
作者：
Carlton SM;Du J;Tan HY;Nesic O;Hargett GL;Bopp AC;Yamani A;Lin Q;Willis WD;Hulsebosch CE
通讯作者：
Hulsebosch CE
DOI：
10.1523/jneurosci.3257-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
通讯作者：
Popovich PG