The core of maintaining neuropathic pain: Crosstalk between glial cells and neurons (neural cell crosstalk at spinal cord)

BACKGROUND: Neuropathic pain (NP) caused by the injury or dysfunction of the nervous system is a chronic pain state accompanied by hyperalgesia, and the available clinical treatment is relatively scarce. Hyperalgesia mediated by pro‐inflammatory factors and chemokines plays an important role in the occurrence and maintenance of NP. DATA TREATMENT: Therefore, we conducted a systematic literature review of experimental NP (PubMed Medline), in order to find the mechanism of inducing central sensitization and explore the intervention methods of hyperalgesia caused by real or simulated injury. RESULT: In this review, we sorted out the activation pathways of microglia, astrocytes and neurons, and the process of crosstalk among them. It was found that in NP, the microglia P2X4 receptor is the key target, which can activate the mitogen‐activated protein kinase pathway inward and then activate astrocytes and outwardly activate neuronal tropomyosin receptor kinase B receptor to activate neurons. At the same time, activated neurons continue to maintain the activation of astrocytes and microglia through chemokines on CXCL13/CXCR5 and CX3CL1/CX3CR1. This crosstalk process is the key to maintaining NP. CONCLUSION: We summarize the further research on crosstalk among neurons, microglia, and astrocytes in the central nervous system, elaborate the ways and connections of relevant crosstalk, and find potential crosstalk targets, which provides a reference for drug development and preclinical research.