Acute pain functions as a defense mechanism in the body, while chronic pain has negative adverse effects on the body over time, including changes in mood, depression, sleep disturbances, and impaired immune mechanisms.  It is believed that the prolongation of pain primarily involves dysfunction of the neural network, but the detailed mechanism remains to be elucidated. The elucidation of these mechanisms is important not only for the development of therapeutic strategies for pain relief, but also for understanding systemic afferent and efferent neural network linkages. Because pain control mechanisms are based on an integrated balance of highly complex networks, we expect that chronic and prolonged pain can also be caused by slight dysregulation of the network that transmits pain. Therefore, it is necessary to analyze in detail the temporal and spatial changes in the cells that respond to pain. On the other hand, it has been shown in clinical practice that residual pain significantly worsens the prognosis of various diseases, so excessive pain signals can alter immune cell responses through systemic neural networks and induce weakening of the organism. In this symposium, we focus on the negative effects of chronic pain on the immune system and other biohomeostatic mechanisms on severe pain.