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Biomed Pharmacother ; 125: 110017, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32106384

RESUMO

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.


Assuntos
Dor Crônica/metabolismo , Quinases da Família src/metabolismo , Animais , Biomarcadores , Proteínas de Transporte/metabolismo , Dor Crônica/tratamento farmacológico , Dor Crônica/etiologia , Suscetibilidade a Doenças , Tolerância a Medicamentos , Humanos , Imunomodulação , Microglia/imunologia , Microglia/metabolismo , Terapia de Alvo Molecular , Morfina/metabolismo , Morfina/farmacologia , Morfina/uso terapêutico , Plasticidade Neuronal/genética , Ligação Proteica , Receptores de N-Metil-D-Aspartato/metabolismo , Transdução de Sinais , Quinases da Família src/antagonistas & inibidores
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