Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
School of Human and Social Sciences, University of West London, London, UK.
Biomed Pharmacother. 2020 May;125:110017. doi: 10.1016/j.biopha.2020.110017. Epub 2020 Feb 25.
Despite the growing knowledge of the mechanisms of chronic pain, the treatment of this disorder in the clinic remains a major challenge. Src-family protein tyrosine kinases (SFKs), a group of non-receptor protein tyrosine kinases, have been implicated in neuronal development and synaptic plasticity. SFKs are critical for the regulate of N-methyl-D-aspartic acid receptor (NMDAR) 2B subunit phosphorylation by various transmembrane receptors, e.g., G-protein coupled receptors (GPCRs), EphB receptors (EphBRs), increased intracellular calcium, epidermal growth factor (EGF) and other growth factors, and thus contribute to the development of chronic pain. SFKs have also been regarded as important points of convergence of intracellular signalling components for the regulation of microglial functions and the immune response. Additionally, the intrathecal administration of SFK inhibitors significantly alleviates mechanical allodynia in different chronic pain models. Here, we reviewed the current evidence for the role of SFKs in the development of chronic pain caused by complete Freund's adjuvant (CFA) injection, peripheral nerve injury (PNI), streptozotocin (STZ) injection and bone metastasis. Moreover, the role of SFKs in the development of morphine tolerance is also discussed. The regulation of SFKs therefore has emerged as a potential therapeutic target for the treatment of chronic pain in terms of safety and efficacy.
尽管人们对慢性疼痛的机制有了越来越多的了解，但临床上这种疾病的治疗仍然是一个主要挑战。Src 家族蛋白酪氨酸激酶（SFKs）是一组非受体蛋白酪氨酸激酶，已被牵涉到神经元发育和突触可塑性中。SFKs 对于各种跨膜受体（例如 G 蛋白偶联受体（GPCR）、EphB 受体（EphBR）、细胞内钙离子增加、表皮生长因子（EGF）和其他生长因子）调节 N-甲基-D-天冬氨酸受体（NMDAR）2B 亚基磷酸化至关重要，从而有助于慢性疼痛的发展。SFKs 也被认为是调节小胶质细胞功能和免疫反应的细胞内信号成分的重要汇聚点。此外，鞘内给予 SFK 抑制剂可显著减轻不同慢性疼痛模型中的机械性痛觉过敏。在这里，我们综述了 SFKs 在完全弗氏佐剂（CFA）注射、周围神经损伤（PNI）、链脲佐菌素（STZ）注射和骨转移引起的慢性疼痛发展中的作用。此外，还讨论了 SFKs 在吗啡耐受发展中的作用。SFKs 的调节因此已成为治疗慢性疼痛的潜在治疗靶点，在安全性和疗效方面具有优势。
