Abstract
Background: Chronic pain and fatigue are two cardinal features of ankylosing spondylitis (AS) and how to effectively treat these conditions continues to be a challenge. The underlying mechanisms and the relationship between AS-related pain and fatigue remain poorly understood. The present study was conducted, therefore, to explore the brain functional and structural changes associated with pain and fatigue in AS.Methods: A total of 65 AS patients (48 men and 17 women; 32.33 ± 8.6 years) and 53 age- and sex-matched controls were enrolled in the study. The patients underwent clinical assessment based on Total Back Pain scores, Fatigue Severity Scale, Bath Ankylosing Spondylitis Disease Activity Index, (BASDAI), high-sensitivity C-reactive Protein (hsCRP), erythrocyte sedimentation rate (ESR), and Beck Depression Inventory (BDI). Using 3T magnetic resonance imaging (3T-MRI), we analyzed the brain functional (connectivity and nodal properties) and structural (covariance and gray matter volumes) differences between AS patients and controls. Furthermore, we extracted the values of the significantly changed regions in the AS cohort and explored their association with pain and fatigue.Results: In AS patients, there were functional and structural abnormalities distributed in the default mode network (DMN), salience network (SN), sensory/somatomotor network (SMN), dorsal attention network (DAN), task control network (TCN), and visual network, and some regions showed both types of changes. Among these, the functional connectivity (FC) between the left insula and medial prefrontal cortex, the betweenness centrality of the left medial prefrontal cortex and the gray matter volume of the right putamen tracked both pain and fatigue. In addition, pain was related to within-DMN FC disruption and nodal function / gray matter volumes changes in DMN, SN, and the visual network, while fatigue mainly involved the SMN, DAN, and TCN. Moreover, certain changes were also related to BASDAI and inflammation level.Conclusion: This study offers new insights into understanding the neural mechanism of AS-related pain and fatigue, and could help to stratify patients based on the correlation features and ultimately move towards a personalized therapy.
Highlights
Ankylosing spondylitis (AS) is an immune-mediated systemic inflammatory disease that mainly affects the spine and sacroiliac joint and is characterized as inflammatory low back pain [1]
To exclude possible determinants of AS-related pain, we conducted multiple regression analyses controlling for age and gender, where Fatigue Severity Scale (FSS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), hsCRP, ESR, and BDI were selected as the dependent variables
Our key findings were: (i) there were multiple pain and fatigue-related FC changes in several key regions belonging to the default mode network (DMN), salience network (SN), SSN, and dorsal attention network (DAN); (ii) AS-related pain mainly involved the DMN, SN, and visual networks, while fatigue was associated with the DMN, sensorimotor network (SMN), and DAN; (iii) some of the above changes could, at least in part, be explained by underlying structural alterations; and (iv) there were both distinct and overlapping functional and structural abnormalities correlated with pain and fatigue, reflecting the multifactorial nature of the two symptoms of AS at a neurobiological level
Summary
Ankylosing spondylitis (AS) is an immune-mediated systemic inflammatory disease that mainly affects the spine and sacroiliac joint and is characterized as inflammatory low back pain [1]. Pain is a central element of the widely used clinical measure of AS activity known as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) [2], and evaluating pain relief is a recognized primary outcome in the assessment of treatment response in AS studies. Chronic pain and fatigue are two cardinal features of ankylosing spondylitis (AS) and how to effectively treat these conditions continues to be a challenge. The underlying mechanisms and the relationship between AS-related pain and fatigue remain poorly understood. The present study was conducted, to explore the brain functional and structural changes associated with pain and fatigue in AS
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