Clinical phenotype matters: structural and functional thalamic changes in neuropathic low-back pain

Neuropathic chronic low-back pain (neuCLBP) is associated with worse clinical outcomes compared with non-neuropathic or axial CLBP (non-neuCLBP) and has limited effective nonsurgical treatment options, reflecting poor understanding of its underlying pathophysiology. In this study, we compared neuCLBP and non-neuCLBP patients using standardized clinical phenotyping of the neuropathic component alongside multimodal brain functional magnetic resonance imaging (fMRI). We hypothesized that, consistent with the definition of neuropathic pain as pain arising from injury to the somatosensory nervous system, neuCLBP patients would exhibit reduced thalamic volume and/or altered thalamic shape, reduced primary somatosensory cortex (S1) thickness, and altered resting-state functional connectivity of these structures compared with non-neuCLBP patients and pain-free healthy controls. Consistent with previous literature, we observed that neuCLBP patients (n = 28) presented with more severe clinical symptoms than non-neuCLBP patients (n = 28). Structurally, neuCLBP patients exhibited extensive differences in thalamic shape but no significant differences in thalamic volume or S1 gray matter thickness. By contrast, by examining resting-state thalamic connectivity gradient maps, we found that non-neuCLBP patients exhibited the most pronounced alterations in these gradients. This study is the first to combine multimodal fMRI with rigorous, standardized phenotyping to investigate neuCLBP. While our results may be influenced by greater symptom severity in the neuCLBP patients, they indicate that these patients may display distinct central plasticity patterns. The findings also highlight the importance of distinguishing between these clinical phenotypes to reduce heterogeneity in future studies.