糖皮质激素在慢性疼痛中的双重作用机制

The Dual Role of Glucocorticoids in Chronic Pain

糖皮质激素(glucocorticoid,GC)是下丘脑-垂体-肾上腺(hypothalamic-pituitary-adrenal,HPA)轴分泌的最终效应激素,通过与糖皮质激素受体(glucocorticoid receptors,GR)结合行使功能。研究发现,GC在慢性疼痛中表现双重作用,内源性GC作为抗炎类固醇通过募集免疫细胞、抑制激酶通路、调节神经胶质细胞在部分类型的神经病理性疼痛及炎性痛中发挥抑痛作用,但在应激情况下,GC水平异常升高参与中枢神经系统神经元的凋亡、兴奋、记忆等,通过调控不同的信号反应或微环境促进病理性疼痛。本文综述GC在慢性疼痛中的作用,了解其发挥镇痛或致痛的双重作用机制。

Glucocorticoid(GC) was the final effect hormone in hypothalamic-pituitary adrenal(HPA) axis.Pain,disease,and stress can trigger increased GC expression.Depending on the peripheral area innervated by the nerve,the type of pain,and the stress stimulus,GC has been shown to be both injury-promoting and injury-resisting in chronic pain.In the context of chronic pain,GC induces the structural plasticity of neurons,schwann cells,microglia,oligodendrocytes and astrocytes through its interaction with glucocorticoid receptors(GR),which participate in the apoptosis,excitation and memory of neurons and immune cells of the nervous system,causing pain behavior to decrease or increase.GC is mainly expressed at a relatively high baseline in the central neuronal system,especially the hippocampus,cortex and spinal cord,under stress or non-stressconditions.However,the plasticity of neurons or immune cells induced by stress is usually poor.Meanwhile,the induced GC overexpression induces and enhances chronic pain through different signaling pathways,and associated with neuropsychiatric diseases such as depression.In addition,understanding the dual analgesic or pain-inducing mechanisms of GC in chronic pain should focus on determining how GC acts on different cell types in the peripheral and central nervous systems.At the same time,further research on the dual mechanism of GC in the central nervous system will undoubtedly contribute to the treatment of chronic pain and have obvious clinical significance.