Abstract：
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.
摘要：
病理性疼痛在临床实践和研究中提出了重大挑战。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。这篇综述探讨了AQP4与疼痛相关疾病之间的关系。包括癌症疼痛，神经性疼痛,和炎性疼痛。在癌症疼痛中，肿瘤细胞中AQP4表达上调与疼痛严重程度增加有关，可能通过肿瘤诱导的炎症和水肿。靶向AQP4可能为管理癌症疼痛提供治疗策略。还发现AQP4在神经损伤中起作用。在脑和脊髓的疼痛相关区域检测到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缺陷小鼠表现出减少的慢性疼痛反应，提示AQP4可能参与慢性疼痛调节，AQP4参与炎症时的疼痛调节，因此，了解AQP4介导的疼痛调节可能会导致新的抗炎和镇痛治疗。磁共振成像（MRI）技术的最新进展能够评估AQP4的表达和定位，有助于我们了解其参与脑水肿和与病理性疼痛相关的清除途径。此外，通过基因疗法和小分子调节剂靶向AQP4有望成为一种潜在的治疗干预措施.未来的研究应集中在利用先进的MRI技术观察淋巴系统的变化以及脑脊液和间质液的交换。此外,研究非编码RNA对AQP4的调控和探索新型小分子药物是未来研究的重要方向。本文综述了基于AQP4的病理性疼痛治疗创新治疗策略。深蓝色细胞代表星形胶质细胞，绿色细胞代表小胶质细胞，红色代表大脑微脉管系统。
