INFLUENCE OF REPEATED SOCIAL DEFEAT STRESS IN THE NEURAL ACTIVITY OF THE SPINAL DORSAL HORN OF MICE

Social stress is a major risk factor for psychiatric disorders such as depression and anxiety. Negative emotions associated with depression are known to exacerbate pain sensitivity. Several studies demonstrated that depressive-like states are accompanied by reduced pain thresholds. We investigated stress-induced mechanical hypersensitivity by examining SDH neuronal activity and the noradrenergic LC–ACC pathway in mice. Eight-week-old male C57BL/6J mice were used in this study. cSDS was induced by daily 10-min physical confrontations with an aggressive ICR male mouse, followed by 24-h sensory contact through a perforated acrylic divider, repeated for five consecutive days. Pathway-specific manipulation of the LC–ACC circuit was achieved using chemogenetic approaches (DREADDs). Mechanical pain thresholds were assessed using the von Frey test. Neuronal activity in the SDH evoked by mechanical stimulation was recorded under anesthesia using tungsten microelectrodes. cSDS induced a significant reduction in mechanical pain thresholds, which persisted after the cessation of stress exposure. Neuronal responses in the SDH to hindpaw mechanical stimulation were significantly enhanced in cSDS mice compared with controls. Chemogenetic inhibition of the LC–ACC pathway resulted in a further decrease in mechanical pain thresholds. Consistently, suppression of this pathway significantly augmented SDH neuronal activity evoked by mechanical stimulation relative to control conditions. These findings demonstrate that functional impairment of the LC–ACC noradrenergic pathway induced by chronic social stress weakens descending pain inhibitory control from the brain to the spinal cord, leading to mechanical hypersensitivity.