Journal Club 2026.06.18

Psychological stress delays inflammatory resolution and promotes sustained sensory sensitization during recovery from atopic dermatitis

Qiaofeng Zhao, Alberto Leguina-Ruzzi, Mitsutoshi Tominaga, Yayoi Kamata, Atsuko Kamo, Huiying Wan, Yuping Ran, Kenji Takamori

Atopic dermatitis (AD) is a chronic inflammatory disorder characterized by pruritus, eczematous
lesions, and epidermal barrier dysfunction, with substantial impact on quality of life (Weidinger
and Novak 2016). Its pathogenesis reflects a complex interplay between barrier impairment,
immune dysregulation, and environmental triggers, resulting in heterogeneous phenotypes (Kim,
Kim et al. 2019). While mechanisms driving onset and exacerbation have been extensively studied,
the processes governing disease resolution remain poorly understood. Inflammatory resolution is
increasingly recognized as an active process involving immune reprogramming, tissue repair, and
restoration of homeostasis rather than a passive decline in inflammation (Oetjen, Mack et al. 2017).
Disruption of this process may contribute to persistent symptoms and chronic disease activity.
However, the factors that impair inflammatory resolution in AD remain poorly understood.
Psychological stress is a recognized modifier of AD, associated with worsened pruritus and disease
persistence. Experimental incorporation of stress paradigms has improved the translational
relevance of AD models (Hall, Cruser et al. 2012). Restraint stress (RS), a model of psychological
stress in rodents, activates the hypothalamic-pituitary-adrenal (HPA) axis and may enhance DRG
neuronal excitability through glucocorticoid and sympathetic signaling, thereby facilitating Aβ
fiber–mediated mechanical alloknesis (Buynitsky and Mostofsky 2009). However, prior work has
focused largely on stress during active inflammation, emphasizing exacerbation rather than
recovery. We hypothesized that psychological stress disrupts the transition to resolution without
amplifying peak inflammation, thereby sustaining sensory sensitization during recovery.