Functional brain network alterations in neuropathic pain after spinal cord injury: A systematic review

Neuropathic pain (NP) is a common and debilitating complication of spinal cord injury (SCI). Emerging evidence implicates large-scale brain network dysfunction in SCI-NP, but the specific patterns of altered connectivity and their relevance to neuromodulation remain uncertain. This systematic review summarised resting-state functional MRI (rsfMRI) studies examining brain network alterations in SCI-NP. Original human studies using rsfMRI to assess brain functional connectivity in SCI-NP with a comparator group, either healthy controls or SCI participants without NP, were included in the primary synthesis. Data on neuroimaging methodology, seed regions, analysis techniques, connectivity findings, and associations with pain severity were extracted. Study quality was assessed using the Newcastle-Ottawa Scale. Eight controlled studies were included in the primary synthesis. Across these publications, 220 SCI-NP participants, 41 SCI participants without NP, and 152 healthy controls were reported, although some cohorts may have overlapped. Preliminary evidence suggested recurring involvement of insular, thalamocortical, salience, limbic, sensorimotor, default mode, central executive, and descending modulatory circuits. However, findings varied by comparator group, cohort characteristics, and analytic method, and fALFF/PSD findings reflected regional spontaneous activity rather than connectivity. These findings support a network-based framework for understanding SCI-NP but do not establish a reproducible biomarker or validated neuromodulation target. Future studies should use larger longitudinal cohorts, standardised imaging methods, and prospective trials to test whether connectivity-guided neuromodulation can modify network function and improve pain outcomes.