Purpose Chronic low back pain (CLBP) is one of the most important pain disorders with increasing social and economic implications. Given that CLBP is a multidimensional process associated with comorbidities such as anxiety and depression, treatment of chronic low back pain is still a challenge. Advancement of in vivo brain imaging technologies has revealed increasing insights into the etiology and pathogenesis of chronic pain; however, the exact mechanisms of chronification of LBP remain still unclear. The purpose of the present study was to analyse the neurostructural alterations in CLBP and to evaluate the role of comorbidities and their neurostructural underpinnings.Methods In the present study we investigated a wellcharacterized group of 14 patients with CLBP and 14 healthy controls applying structural MRI and psychometric measures. Using an improved algorithm for brain normalization (DARTEL) we performed a voxel-based morphometry (VBM) approach. Correlation analyses were performed to evaluate the role of anxiety and depression in neurostructural alterations observed in CLBP. Results The psychometric measures revealed significantly higher scores on depression and anxiety in the patient population. VBM analysis showed significant decreases in grey matter density in areas associated with pain processing and modulation, i.e. the dorsolateral prefrontal cortex, the thalamus and the middle cingulate cortex. With respect to anxiety and depression scores, we did not observe any correlations to the structural data. Conclusions In the present study we found compelling evidence for alterations of grey matter architecture in CLBP in brain regions playing a major role in pain modulation and control. Our results fit the hypothesis of a ''brain signature'' in chronic pain conditions. The results of the psychometric assessment underline the importance of an interdisciplinary therapeutic approach including orthopedic, neurological and psychological evaluation and treatment.Keywords Chronic low back pain Á MRI Á Voxel based morphometry Á Dorsolateral prefrontal cortex Á Thalamus

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