Department of Neuroscience and Physiology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul 08826, Republic of Korea.
Nanoscale. 2019 Oct 25;11(41):19437-19447. doi: 10.1039/c9nr02648g.
Neuropathic pain is a chronic and pathological pain caused by injury or dysfunction in the nervous system. Pro-inflammatory microglial activation with aberrant reactive oxygen species (ROS) generation in the spinal cord plays a critical role in the development of neuropathic pain. However, the efficacy of current therapeutic methods for neuropathic pain is limited because only neurons or neural circuits involved in pain transmission are targeted. Here, an effective strategy to treat pain hypersensitivity using microglia-targeting ceria-zirconia nanoparticles (CZ NPs) is reported. The CZ NPs are coated with microglia-specific antibodies to promote their delivery to microglia, and thus to improve their therapeutic efficacy. The targeted delivery facilitates the elimination of both pro-inflammatory cytokines and ROS in microglia, enabling the rapid and effective inhibition of microglial activation. As a result, greatly ameliorated mechanical allodynia is achieved in a spinal nerve transection (SNT)-induced neuropathic pain mouse model, proving the potent analgesic effect of the microglia-targeting CZ NPs. Given the generality of the approach used in this study, the microglia-targeting CZ NPs are expected to be useful for the treatment of not only neuropathic pain but also other neurological diseases associated with the vicious activation of microglia.
神经病理性疼痛是由神经系统损伤或功能障碍引起的慢性病理性疼痛。脊髓中促炎小胶质细胞的激活伴随着异常活性氧（ROS）的产生，在神经病理性疼痛的发展中起着关键作用。然而，目前治疗神经病理性疼痛的方法效果有限，因为仅针对涉及疼痛传递的神经元或神经回路。在这里，报道了一种使用针对小胶质细胞的铈锆纳米粒子（CZ NPs）治疗疼痛敏感性的有效策略。CZ NPs 被包裹在小胶质细胞特异性抗体上，以促进其递送至小胶质细胞，从而提高其治疗效果。靶向递送有助于消除小胶质细胞中的促炎细胞因子和 ROS，从而快速有效地抑制小胶质细胞的激活。因此，在脊髓神经横断（SNT）诱导的神经病理性疼痛小鼠模型中，实现了机械性痛觉过敏的显著改善，证明了针对小胶质细胞的 CZ NPs 的强大镇痛作用。鉴于本研究中使用的方法具有普遍性，预计针对小胶质细胞的 CZ NPs 不仅可用于治疗神经病理性疼痛，还可用于治疗与小胶质细胞恶性激活相关的其他神经疾病。
