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Mohamad Sahebalam, Boshra Hatef, Gila Pirzad Jahromi Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Tehran, 14359-15381, IranCorrespondence: Boshra Hatef, Neuroscience Research Center, Baqiyatallah University of Medical Sciences, Sheikh Bahaei Street, Tehran, 14359-15381, Iran, Email boshrahatef@bmsu.ac.irBackground: Central sensitization (CS) is increasingly recognized as a key mechanism underlying chronic low back pain (CLBP), and has been linked to disturbed sleep, psychological distress, altered hypothalamic–pituitary–adrenal (HPA) axis function, low-grade inflammation, and cognitive dysfunction. However, few studies have simultaneously examined these domains in patients with different levels of CS compared with pain-free individuals.Methods: In this cross-sectional study, adults with CLBP were classified into severe and mild CS groups using the Central Sensitization Inventory and were compared with healthy controls. Sleep quality, psychological distress, and pain-related cognition were assessed using the Pittsburgh Sleep Quality Index, Depression Anxiety Stress Scales-21, and pain measures. Morning salivary cortisol, interleukin-6 (IL-6), and fasting blood glucose were obtained as biological markers, and cognitive performance was evaluated using the Corsi Block-Tapping and Tower of London tasks. Group differences were analyzed using one-way ANOVA with Tukey post-hoc tests.Results: Forty-two participants (patients with CLBP and pain-free controls) completed the study. Compared with both mild CS patients and controls, the severe CS group showed markedly poorer sleep quality and higher levels of psychological distress. Morning cortisol concentrations were significantly elevated only in the severe CS group, whereas no statistically significant differences were detected for fasting glucose or IL-6 between groups. On the Corsi Block-Tapping task, healthy controls outperformed both CS groups, indicating reduced visuospatial working memory in patients, whereas no significant group differences were observed on the Tower of London planning task.Conclusion: Severe central sensitization in CLBP is associated with poor sleep, increased emotional distress, elevated morning cortisol, and deficits in visuospatial working memory, even in the absence of clear differences in IL-6 or fasting glucose. These findings support a biopsychosocial profile characterized by both neuroendocrine and cognitive alterations in patients with high levels of CS and highlight potential targets for multimodal assessment and intervention.Plain Language Summary: Chronic low back pain is very common and often does not respond well to usual treatments. One important reason may be “central sensitization”, which means that the brain and spinal cord become overly sensitive and keep amplifying pain signals. People with chronic pain and central sensitization often also have poor sleep, emotional distress, and problems with thinking skills, but these relationships are not fully understood.In this study, we examined adults with non-specific chronic low back pain who attended orthopedic clinics. We divided them into two groups based on their score on the Central Sensitization Inventory: a high central sensitization group and a low central sensitization group. We measured sleep quality, symptoms of depression, anxiety, and stress, morning levels of the stress hormone cortisol, inflammatory and metabolic markers (interleukin-6 and fasting blood glucose), and performance on tests of visuospatial working memory and planning.People with high central sensitization reported worse sleep and higher emotional distress. They also showed higher morning cortisol levels and slightly poorer visuospatial working memory. In contrast, interleukin-6 and fasting blood glucose did not clearly differ between the groups. These findings suggest that poor sleep, psychological distress, stress-system changes, and subtle cognitive problems are important features of chronic low back pain with central sensitization, and they should be considered in assessment and treatment.Keywords: central sensitization, chronic low back pain, cognitive function, cortisol, interleukin-6, psychological distress, sleep quality