Reorganization of functional brain network architecture in chronic osteoarthritis pain

Abstract

Osteoarthritis (OA) manifests with chronic pain, motor impairment, and proprioceptive changes. However, the role of the brain in the disease is largely unknown. Here, we studied brain networks using the mathematical properties of graphs in a large sample of knee and hip OA (KOA, n = 91; HOA, n = 23) patients. We used a robust validation strategy by subdividing the KOA data into discovery and testing groups and tested the generalizability of our findings in HOA. Despite brain global topological properties being conserved in OA, we show there is a network wide pattern of reorganization that can be captured at the subject‐level by a single measure, the hub disruption index. We localized reorganization patterns and uncovered a shift in the hierarchy of network hubs in OA: primary sensory and motor regions and parahippocampal gyrus behave as hubs and insular cortex loses its central placement. At an intermediate level of network structure, frontoparietal and cingulo‐opercular modules showed preferential reorganization. We examined the association between network properties and clinical correlates: global disruption indices and isolated degree properties did not reflect clinical parameters; however, by modeling whole brain nodal degree properties, we identified a distributed set of regions that reliably predicted pain intensity in KOA and generalized to hip OA. Together, our findings reveal that while conserving global topological properties, brain network architecture reorganizes in OA, at both global and local scale. Network connectivity related to OA pain intensity is dissociated from the major hub disruptions, challenging the extent of dependence of OA pain on nociceptive signaling.

Dynamic Functional Brain Reconfiguration During Sustained Pain

“…Also, considering that subcortical structures, such as the thalamus, are important for the early processing of nociceptive signals from the peripheral nervous system, our finding suggests that the recruitment of both bottom-up (subcortical) and top-down (frontoparietal) systems and their integration are crucial to the conscious experience of sustained pain. Previous studies that reported modular reorganization of the somatomotor network (H Mano et al, 2018) and frontoparietal network (Barroso et al, 2021;H Mano et al, 2018) in chronic pain are also in line with our results. Importantly, this systems-level integration occurred in a somatotopy-specific way-the SVM classifier (Figure 4) showed that the ventral primary somatomotor area, which subserves tongue sensation, was segregated from the other somatomotor regions and integrated with the subcortical regions during the early period of pain.…”

Gout Is Not Just Arthritis: Abnormal Cortical Thickness and Structural Covariance Networks in Gout

“…The left parahippocampal cortex is one of the hubs in gout patients group discovered in this study. Similar results were reported in previous studies on the functional brain network of osteoarthritis, in a region that was thought to be related to the response to analgesics ( 56 , 57 ). The insular cortex is considered essential for the perception, modulation, and chronification of pain ( 58 ).…”

The Recovery of Cognitive and Affective Deficiencies Linked with Chronic Osteoarthritis Pain and Implicated Pathways by Slow-Releasing Hydrogen Sulfide Treatment

“…The anterior cingulate cortex is a region involved in executive, attention, and decisionmaking processes [52]. Previous studies have reported a direct association between the presence of chronic pain and linked memory loss in this area [39,53,54]. In our pain model, an increased expression of PI3K was observed in the anterior cingulate cortex, which was only reversed by GYY4137 treatment.…”