Division of Pharmacology "L. Donatelli," Department of Experimental Medicine, Second University of Naples Naples, Italy.
Front Integr Neurosci. 2011 Dec 1;5:79. doi: 10.3389/fnint.2011.00079. eCollection 2011.
Neuropathic pain (NP) is an incurable disease caused by a primary lesion in the nervous system. NP is a progressive nervous system disease that results from poorly defined neurophysiological and neurochemical changes. Its treatment is very difficult. Current available therapeutic drugs have a generalized nature, sometime acting only on the temporal pain properties rather than targeting the several mechanisms underlying the generation and propagation of pain.
Using biomolecular and immunohistochemical methods, we investigated the effect of the systemic injection of human mesenchymal stem cells (hMSCs) on NP relief. We used the spared nerve injury (SNI) model of NP in the mouse. hMSCs were injected into the tail vein of the mouse. Stem cell injection was performed 4 days after sciatic nerve surgery. Neuropathic mice were monitored every 10 days starting from day 11 until 90 days after surgery.
hMSCs were able to reduce pain-like behaviors, such as mechanical allodynia and thermal hyperalgesia, once injected into the tail vein. An anti-nociceptive effect was detectable from day 11 post surgery (7 days post cell injection). hMSCs were mainly able to home in the spinal cord and pre-frontal cortex of neuropathic mice. Injected hMSCs reduced the protein levels of the mouse pro-inflammatory interleukin IL-1β and IL-17 and increased protein levels of the mouse anti-inflammatory interleukin IL-10, and the marker of alternatively activated macrophages CD106 in the spinal cord of SNI mice.
As a potential mechanism of action of hMSCs in reducing pain, we suggest that they could exert their beneficial action through a restorative mechanism involving: (i) a cell-to-cell contact activation mechanism, through which spinal cord homed hMSCs are responsible for switching pro-inflammatory macrophages to anti-inflammatory macrophages; (ii) secretion of a broad spectrum of molecules to communicate with other cell types. This study could provide novel findings in MSC pre-clinical biology and their therapeutic potential in regenerative medicine.
神经性疼痛（NP）是一种由神经系统原发性损伤引起的无法治愈的疾病。NP 是一种进行性神经系统疾病，源于未明确的神经生理和神经化学变化。其治疗非常困难。目前可用的治疗药物具有普遍性，有时仅对暂时的疼痛性质起作用，而不是针对疼痛产生和传播的几种机制。
我们使用生物分子和免疫组织化学方法研究了全身注射人骨髓间充质干细胞（hMSCs）对 NP 缓解的影响。我们使用了小鼠的 spared nerve injury（SNI）NP 模型。hMSCs 被注入小鼠的尾静脉。在坐骨神经手术后 4 天进行干细胞注射。从手术第 11 天开始，每 10 天监测一次神经病理性小鼠，直到手术后 90 天。
hMSCs 一旦注入尾静脉，就能减轻类似疼痛的行为，如机械性痛觉过敏和热痛觉过敏。术后第 11 天（细胞注射后第 7 天）即可检测到抗伤害作用。hMSCs 主要能够归巢到神经病理性小鼠的脊髓和前额叶皮层。注射的 hMSCs 降低了小鼠促炎白细胞介素 IL-1β 和 IL-17 的蛋白水平，增加了脊髓中抗炎白细胞介素 IL-10 和交替激活巨噬细胞 CD106 的蛋白水平。
作为 hMSCs 减轻疼痛的潜在作用机制，我们认为它们可以通过一种恢复性机制发挥其有益作用，该机制包括：（i）细胞间接触激活机制，通过该机制，归巢到脊髓的 hMSCs 负责将促炎巨噬细胞转换为抗炎巨噬细胞；（ii）分泌广泛的分子与其他细胞类型进行通讯。这项研究为 MSC 临床前生物学及其在再生医学中的治疗潜力提供了新的发现。
