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.