Anesthesiology Department, The First Affiliated Hospital of Ningbo University, Ningbo, China.
Health Science Center, Ningbo University, Ningbo, China.
Cell Mol Neurobiol. 2023 Nov;43(8):3997-4005. doi: 10.1007/s10571-023-01422-9. Epub 2023 Oct 21.
Pathological pain presents significant challenges in clinical practice and research. Aquaporin-4 (AQP4), which is primarily found in astrocytes, is being considered as a prospective modulator of pathological pain. This review examines the association between AQP4 and pain-related diseases, including cancer pain, neuropathic pain, and inflammatory pain. In cancer pain, upregulated AQP4 expression in tumor cells is linked to increased pain severity, potentially through tumor-induced inflammation and edema. Targeting AQP4 may offer therapeutic strategies for managing cancer pain. AQP4 has also been found to play a role in nerve damage. Changes in AQP4 expression have been detected in pain-related regions of the brain and spinal cord; thus, modulating AQP4 expression or function may provide new avenues for treating neuropathic pain. Of note, AQP4-deficient mice exhibit reduced chronic pain responses, suggesting potential involvement of AQP4 in chronic pain modulation, and AQP4 is involved in pain modulation during inflammation, so understanding AQP4-mediated pain modulation may lead to novel anti-inflammatory and analgesic therapies. Recent advancements in magnetic resonance imaging (MRI) techniques enable assessment of AQP4 expression and localization, contributing to our understanding of its involvement in brain edema and clearance pathways related to pathological pain. Furthermore, targeting AQP4 through gene therapies and small-molecule modulators shows promise as a potential therapeutic intervention. Future research should focus on utilizing advanced MRI techniques to observe glymphatic system changes and the exchange of cerebrospinal fluid and interstitial fluid. Additionally, investigating the regulation of AQP4 by non-coding RNAs and exploring novel small-molecule medicines are important directions for future research. This review shed light on AQP4-based innovative therapeutic strategies for the treatment of pathological pain. Dark blue cells represent astrocytes, green cells represent microglia, and red ones represent brain microvasculature.
病理性疼痛在临床实践和研究中带来了重大挑战。水通道蛋白 4（AQP4）主要存在于星形胶质细胞中，被认为是病理性疼痛的潜在调节剂。本综述探讨了 AQP4 与疼痛相关疾病之间的关联，包括癌症疼痛、神经性疼痛和炎症性疼痛。在癌症疼痛中，肿瘤细胞中 AQP4 表达的上调与疼痛严重程度的增加有关，这可能是通过肿瘤诱导的炎症和水肿实现的。靶向 AQP4 可能为管理癌症疼痛提供治疗策略。AQP4 还被发现与神经损伤有关。在与疼痛相关的大脑和脊髓区域检测到 AQP4 表达的变化；因此，调节 AQP4 的表达或功能可能为治疗神经性疼痛提供新的途径。值得注意的是，AQP4 缺陷型小鼠表现出慢性疼痛反应的减少，这表明 AQP4 可能参与慢性疼痛的调节，AQP4 参与炎症期间的疼痛调节，因此了解 AQP4 介导的疼痛调节可能导致新型抗炎和镇痛疗法。磁共振成像（MRI）技术的最新进展能够评估 AQP4 的表达和定位，有助于我们理解其在脑水肿和与病理性疼痛相关的清除途径中的作用。此外，通过基因治疗和小分子调节剂靶向 AQP4 显示出作为潜在治疗干预的潜力。未来的研究应侧重于利用先进的 MRI 技术观察糖质内液系统的变化以及脑脊液和细胞间液的交换。此外，研究非编码 RNA 对 AQP4 的调节以及探索新型小分子药物是未来研究的重要方向。本综述为基于 AQP4 的病理性疼痛治疗创新治疗策略提供了思路。深蓝色细胞代表星形胶质细胞，绿色细胞代表小胶质细胞，红色细胞代表脑微血管。
