P2X4 receptor is activated by ATP, opens the ion channels on cell membrane (mainly calcium influx), activates microglia, releases some damaging factors (such as IL-1β, TNF-a, and IL-6), induces and aggravates chronic pain (neuropathic pain, cancer pain, inflammatory pain).

Chronic pain is a common symptom of most clinical diseases, which seriously affects the psychosomatic health of patients and brings some pain to patients. Due to its pathological mechanism is very complicated and the treatment of chronic pain has always been a difficult problem in clinical. Normally, drugs are usually used to relieve pain, but the analgesic effect is not good, especially for cancer pain patients, the analgesic effect is poor. Therefore, exploring the pathogenesis and treatment of chronic pain has aroused the interest of many researchers. A large number of studies have shown that the role of ATP and P2X4 receptor (P2X4R) play an important role in the pathogenesis of chronic pain. P2X4R is dependent on ATP ligand-gated ion channel receptor, which can be activated by ATP and plays an important role in the information transmission of nerve system and the formation of pain. Therefore, in this paper, we comprehensively described the structure and biological functions of P2X4R, and outlined behavioral evaluation methods of chronic pain models. Moreover, we also explored the inherent relationship between P2X4R and chronic pain, and described the therapeutic effect of P2X4R antagonist on chronic pain, and provided some valuable help for the treatment of chronic pain.