Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK.
Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, China.
Br J Anaesth. 2017 Apr 1;118(4):504-516. doi: 10.1093/bja/aex006.
Neuropathic pain, a maladaptive and chronic condition that can develop after a lesion or disease affecting the somatosensory system, is characterized by allodynia, hyperalgesia and spontaneous pain, and comorbidities such as sleep deprivation, depression and anxiety. The activation of microglial cells in response to nerve injury has been implicated in the development of neuropathic pain. Mediators such as Neuregulin-1, matrix metalloproteinase (MMP)-2, MMP-9, The chemokine (C-C motif) ligand 2 (CCL2) and fractalkine are released after nerve injury and are involved in the activation of microglial cells. These activated cells in turn release factors that increase the excitation and decrease the inhibition of interneurons. Microglial cells release factors such as interleukin (IL)-6, IL-1β and tumour necrosis factor-α (TNF-α) that cause the painful symptoms. It is becoming increasingly apparent that an intricate network of cytokines and cellular signalling mechanisms underpin the complex relationship between microglia and various cell types including neurones, astrocytes, oligodendrocytes, mast cells and T-cells. Although the precise mechanism of action of microglial cells in producing neuropathic pain has not been completely elucidated, research into these different activating factors and cytokines is providing further insight into the role of microglial cells in the development and maintenance of neuropathic pain. Further studies also are required to elucidate how "pain" mediators act on neurones and how the interactions between these mediators, or between neurones and glia in the presence of these mediators occur, in order to develop effective therapies for the management of neuropathic pain.
神经病理性疼痛是一种适应性和慢性疾病，可在影响躯体感觉系统的损伤或疾病后发生，其特征为痛觉过敏、痛觉过强和自发性疼痛，以及睡眠剥夺、抑郁和焦虑等合并症。小胶质细胞在神经损伤后的激活被认为与神经病理性疼痛的发展有关。神经调节素 1、基质金属蛋白酶 (MMP)-2、MMP-9、趋化因子 (C-C 基元) 配体 2 (CCL2) 和 fractalkine 等介质在神经损伤后释放，并参与小胶质细胞的激活。这些激活的细胞反过来又释放增加中间神经元兴奋和减少抑制的因子。小胶质细胞释放白细胞介素 (IL)-6、IL-1β 和肿瘤坏死因子-α (TNF-α) 等因子，导致疼痛症状。越来越明显的是，细胞因子和细胞信号转导机制的复杂网络为小胶质细胞与包括神经元、星形胶质细胞、少突胶质细胞、肥大细胞和 T 细胞在内的各种细胞类型之间的复杂关系提供了基础。尽管小胶质细胞在产生神经病理性疼痛中的确切作用机制尚未完全阐明，但对这些不同激活因子和细胞因子的研究正在提供进一步的见解，了解小胶质细胞在神经病理性疼痛的发展和维持中的作用。还需要进一步的研究来阐明“疼痛”介质如何作用于神经元，以及这些介质之间的相互作用，或在存在这些介质的情况下神经元与神经胶质细胞之间的相互作用如何发生，以便为神经病理性疼痛的管理开发有效的治疗方法。
