Zhang Sijia, Kartha Sonia, Lee Jasmine, Winkelstein Beth A
Department of Bioengineering, University of Pennsylvania, 210 S. 33rd Street, 240 Skirkanich Hall, Philadelphia, Pennsylvania 19104, United States.
Department of Physics and Astronomy, University of Pennsylvania, 209 S. 33rd Street, David Rittenhouse Laboratory, Philadelphia, Pennsylvania 19104, United States.
ACS Biomater Sci Eng. 2017 Nov 13;3(11):2744-2760. doi: 10.1021/acsbiomaterials.7b00012. Epub 2017 Mar 7.
Neurotrauma is a common source for a host of neurological disorders, including chronic pain. Pathological changes underlying neural injury and pain are complex due to the multiscale spatiotemporal nature of the nervous system and its response to insults. Understanding the combined influence of tissue mechanics, neuronal and glial activation, and molecular processes on the development and maintenance of pain has recently gained attention. The growing knowledge about nociceptive mechanisms has inspired the design of novel therapeutic materials and compounds for neuronal regulation. Primary mechanical insults and secondary inflammatory responses can induce morphological changes, electrophysiological abnormalities, and altered neurotransmitter release associated with neuronal dysfunction, degeneration, and/or death in both central and peripheral nervous systems. Such responses in afferent and spinal dorsal horn neurons directly and indirectly potentiate pain. Using separate radiculopathy and joint pain models, the mechanical, nociceptive, and inflammatory aspects of pain are reviewed. In that context, biomaterials and compounds with material advantages, neuroprotective benefits, or anti-inflammatory effects to mitigate pain are identified. Several promising techniques to promote neuronal survival and axonal regeneration after injury, including bioactive scaffolds, blocking growth-inhibitory molecules, and active drug delivery, are highlighted. Similar biomaterials-based strategies and molecular intervention have shown promise in attenuating various types of pain. Advancing these and other approaches will help advance and deepen the mechanistic understanding underlying trauma-induced pain across different length scales.
神经创伤是包括慢性疼痛在内的一系列神经系统疾病的常见病因。由于神经系统的多尺度时空特性及其对损伤的反应，神经损伤和疼痛背后的病理变化十分复杂。了解组织力学、神经元和神经胶质细胞激活以及分子过程对疼痛发生和维持的综合影响最近受到了关注。对伤害感受机制的日益了解激发了用于神经元调节的新型治疗材料和化合物的设计。原发性机械损伤和继发性炎症反应可诱导形态学变化、电生理异常以及与中枢和外周神经系统中神经元功能障碍、退化和/或死亡相关的神经递质释放改变。传入神经元和脊髓背角神经元的此类反应直接和间接增强疼痛。本文利用单独的神经根病和关节疼痛模型，对疼痛的机械、伤害感受和炎症方面进行了综述。在此背景下，确定了具有减轻疼痛的材料优势、神经保护作用或抗炎作用的生物材料和化合物。重点介绍了几种促进损伤后神经元存活和轴突再生的有前景的技术，包括生物活性支架、阻断生长抑制分子和主动药物递送。类似的基于生物材料的策略和分子干预在减轻各种类型的疼痛方面已显示出前景。推进这些及其他方法将有助于推进和深化对不同长度尺度上创伤性疼痛潜在机制的理解。
