Emotional Stress Induces Spontaneous Scratching Behavior in Mice in the Absence of an Externally Applied Pruritogen.

BACKGROUND: Pruritus is a prevalent condition that significantly impairs quality of life. Although emotional stress is known to exacerbate pruritus in individuals with skin diseases, its effect on spontaneous scratching behavior in otherwise healthy individuals remains poorly understood. Recent evidence suggests that stress itself may trigger scratching behavior independent of any pruritogenic stimulus. We aimed to determine whether acute stress induces spontaneous scratching in the absence of an externally applied pruritogen and to identify which stressor types are responsible. METHODS: One hundred nine male C57BL/6J mice were assigned to three experiments. Experiment 1 compared spontaneous scratching behavior following 30min of restraint stress with histamine-induced pruritus, including a control group without any cutaneous stimulus. Experiment 2 examined whether physical stress (PS) or emotional stress (ES) contributes to the stress-induced scratching using the Communication Box (C-box) paradigm, with an untreated control and a sham-treated group included for comparison. Experiment 3 measured plasma corticosterone levels by enzyme-linked immunosorbent assay (ELISA) to evaluate the stress responses associated with sham treatment in the C-box. RESULTS: Restraint stress significantly increased scratching behavior, even in the absence of cutaneous stimulation, although the magnitude of this response was lower than that elicited by histamine. Compared with the untreated condition, ES and sham treatment increased scratching behavior, whereas PS produced no significant effect, and the magnitude of this increase was comparable to that induced by restraint stress. Sham treatment in the C-box significantly elevated plasma corticosterone levels relative to naive mice. CONCLUSION: These findings demonstrate that ES induces spontaneous scratching behavior in the absence of an externally applied pruritogen. However, the findings do not support a simple proportional relationship between plasma corticosterone levels and scratching behavior.