Background: Previous studies exploring the anatomical correlates of pain in multiple sclerosis (MS) have relied on structural magnetic resonance imaging (MRI) and descriptive methodologies.

Objective: To establish radiological correlates of neuropathic pain in MS patients through the objective segmentation and analysis of brain MRI.

Methods: This exploratory pilot study included three distinct groups: MS patients with neuropathic pain (n=8), MS patients without pain (n=11), and individuals with small fiber neuropathy (SFN, n=6). Neuropathic pain was confirmed using laser-evoked potentials (LEPs), ensuring an objective assessment of pain function. All participants underwent brain MRI, with MS patients additionally undergoing spinal MRI. Brain region segmentation was conducted using two advanced automated tools: SAMSEG (Sequence Adaptive Multimodal SEGmentation) and SynthSEG. Pain-related brain regions, including the thalamus, brainstem, basal ganglia, prefrontal cortex, and somatosensory cortex, were analyzed and compared amongst the three groups.

Results: The volume of the right pallidum was significantly reduced in MS patients with pain compared to those without pain, as measured by SynthSeg but not with SAMSEG. Individual analysis of regions of interest showed significant results of diffusion tensor imaging analysis in the external capsule, internal capsule, posterior thalamic radiation, and superior longitudinal fasciculus. Quantitative analysis of spinal cord lesions revealed no significant differences between the groups.

Conclusions: These findings highlight a potential of advanced neuroimaging techniques to uncover brain-based correlates of neuropathic pain in MS, though further studies with larger sample sizes are warranted for validation.