Pain- and Fatigue-Related Functional and Structural Changes in Ankylosing Spondylitis: An fRMI Study

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.

Disentangling pain and fatigue in chronic fatigue syndrome: a resting state connectivity study before and after cognitive behavioral therapy

“…Results showed that communication of the SMN with the PMN and DMN was specifically associated with betweenparticipants variance in fatigue across the testing day, over and above the contribution of variance related to pain occurrence, pain disability and CIS-fatigue. This is in line with our hypothesis and previous reports on sensorimotor involvement in fatigue in multiple sclerosis (MS) (Hidalgo de la Cruz et al, 2018), stroke (De Doncker, Dantzer, Ormstad, & Kuppuswamy, 2018;Kuppuswamy, Rothwell, & Ward, 2015), perinatal stroke (Wrightson, Zewdie, Kuo, Millet, & Kirton, 2020) and ankylosing spondylitis (Liu et al, 2020) and generalize our previously reported task-related effects of fatigue (van der Schaaf et al, 2018) to resting-state connectivity. The lack of relationship with CIS-fatigue may relate to the low variability in CIS-fatigue scores as patients were selected to be severely fatigued on this score.…”

“…So far, only a few studies did compare pain and fatigue-related connectivity patterns within one patient population. Specifically, using graph theoretical measures a recent study assessed symptom-specific associations in patients with ankylosing spondylitis and showed a partial network-level dissociation between fatigue-and pain-related brain connectivity (Liu et al, 2020). While functional connectivity of the DMN nodes with the rest of the brain was associated with both pain and fatigue, connectivity of the pre-central gyrus (part of the SMN) and superior parietal gyrus were only associated with fatigue.…”

Alterations in brain structure and function in patients with osteonecrosis of the femoral head: a multimodal MRI study

“…, cognitive coping strategies and attentional distraction) in ONFH patients. In addition, functional and structural changes in the PFC, including ankylosing spondylitis ( Liu et al, 2020 ), irritable bowel syndrome ( Mao et al, 2020 ), chronic lower back pain ( Yu et al, 2020 ), and neuropathic pain ( Li et al, 2020 ), have been demonstrated in other pain studies. In a recent rs-fMRI study ( Feng et al, 2020 ), researchers revealed an abnormal pattern of brain activity in ONFH patients and found that the most significant increase in ALFF occurred in pain-related brain regions, which is consistent with our results.…”

Fatigue in Inflammatory Joint Diseases

“…These regions include the sensory/somatomotor network (SMN), dorsal attention network (DAN), and task control network (TCN). Changes in brain activity and connectivity within these networks may contribute to the experience of fatigue in individuals with AS [85]. Treatment with TNF-alpha inhibitors in patients with AS effectively reduces disease activity and alleviates fatigue.…”