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神经修复治疗缓解神经病理性疼痛并增强感觉轴突再生。

NeuroHeal Treatment Alleviates Neuropathic Pain and Enhances Sensory Axon Regeneration.

机构信息

Institut de Neurociències (INc) and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona (UAB), 08193 Bellaterra, Barcelona, Spain.

Institut Necker Enfants-Malades (INEM), INSERM U1151, Laboratory "Hormonal Regulation of Brain Development and Functions"-Team 8, Université Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France.

出版信息

Cells. 2020 Mar 27;9(4):808. doi: 10.3390/cells9040808.

DOI:10.3390/cells9040808
PMID:32230770
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7226810/
Abstract

Peripheral nerve injury (PNI) leads to the loss of motor, sensory, and autonomic functions, and often triggers neuropathic pain. During the last years, many efforts have focused on finding new therapies to increase axonal regeneration or to alleviate painful conditions. Still only a few of them have targeted both phenomena. Incipient or aberrant sensory axon regeneration is related to abnormal unpleasant sensations, such as hyperalgesia or allodynia. We recently have discovered NeuroHeal, a combination of two repurposed drugs; Acamprosate and Ribavirin. NeuroHeal is a neuroprotective agent that also enhances motor axon regeneration after PNI. In this work, we investigated its effect on sensory fiber regeneration and PNI-induced painful sensations in a rat model of spare nerve injury and nerve crush. The follow up of the animals showed that NeuroHeal treatment reduced the signs of neuropathic pain in both models. Besides, the treatment favored sensory axon regeneration, as observed in dorsal root ganglion explants. Mechanistically, the effects observed in vivo may improve the resolution of cell-protective autophagy. Additionally, NeuroHeal treatment modulated the P2X4-BDNF-KCC2 axis, which is an essential driver of neuropathic pain. These data open a new therapeutic avenue based on autophagic modulation to foster endogenous regenerative mechanisms and reduce the appearance of neuropathic pain in PNI.

摘要

周围神经损伤（PNI）导致运动、感觉和自主功能丧失，常引发神经性疼痛。在过去的几年中，人们致力于寻找新的治疗方法来增加轴突再生或缓解疼痛状况。但只有少数治疗方法能够同时针对这两种现象。起始或异常感觉轴突再生与异常不适感觉有关，如痛觉过敏或感觉异常。我们最近发现了一种名为 NeuroHeal 的组合药物，由两种已重新定位用途的药物（安非他酮和利巴韦林）组成。NeuroHeal 是一种神经保护剂，可促进 PNI 后运动轴突再生。在这项工作中，我们在大鼠备用神经损伤和神经挤压模型中研究了它对感觉纤维再生和 PNI 诱导的疼痛感觉的影响。动物的后续研究表明，NeuroHeal 治疗可减轻两种模型中的神经病理性疼痛症状。此外，该治疗方法有利于感觉轴突再生，在背根神经节外植体中观察到了这一现象。从机制上讲，体内观察到的效果可能会改善细胞保护性自噬的解决。此外，NeuroHeal 治疗还调节了 P2X4-BDNF-KCC2 轴，这是神经性疼痛的一个重要驱动因素。这些数据为基于自噬调节的治疗方法提供了新的途径，以促进内源性再生机制并减少 PNI 中的神经性疼痛出现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59fa/7226810/d7ec48e8afb7/cells-09-00808-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59fa/7226810/9e7813b3a2de/cells-09-00808-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59fa/7226810/5f272e451f71/cells-09-00808-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59fa/7226810/9dc2ae18cf07/cells-09-00808-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59fa/7226810/d9258c852c14/cells-09-00808-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59fa/7226810/d7ec48e8afb7/cells-09-00808-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59fa/7226810/9e7813b3a2de/cells-09-00808-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59fa/7226810/5f272e451f71/cells-09-00808-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59fa/7226810/9dc2ae18cf07/cells-09-00808-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59fa/7226810/d9258c852c14/cells-09-00808-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59fa/7226810/89d8d589de7d/cells-09-00808-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59fa/7226810/d7ec48e8afb7/cells-09-00808-g006.jpg

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2
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3
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Front Physiol. 2022 Dec 15;13:1045520. doi: 10.3389/fphys.2022.1045520. eCollection 2022.
4
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