Distinct preoperative multimodal brain reorganizations underlie differential outcomes of DREZ lesioning for neuropathic pain after spinal cord injury.

Dorsal root entry zone (DREZ) lesioning is an established neurosurgical procedure for treating refractory neuropathic pain (NP) after spinal cord injury (SCI). To identify preoperative neuroimaging biomarkers associated with surgical outcomes, we analyzed 24 SCI-NP participants who showed differential responses to DREZ lesioning. We hypothesized that preoperative alterations in white matter integrity, brain structure, and functional connectivity (FC), particularly within the descending pain modulatory system, would differ between participants with effective versus ineffective surgical outcomes. Based on the extent of postoperative pain relief, participants were classified into an effective group (EG) and an ineffective group (IG). Preoperative multimodal MRI was obtained, including diffusion tensor imaging (DTI), 3D high-resolution T1-weighted structural imaging (extending to the cervical 5 level), and resting-state functional data. Cervical level C2/C3 macrostructure parameters were measured employing the Jim 7.0 software. Tract-based spatial statistics was performed on DTI data, and voxel-based morphometry was carried out for structural images. For functional MRI data, regions showing significant structural alterations were used as seeds to compute FC. Compared to the EG, the IG exhibited increased mean diffusivity (MD) in the bilateral internal capsule and axial diffusivity (AD) in the right corticospinal tract, along with increased gray matter volume in the periaqueductal gray (PAG). Using the PAG as a seed, the IG showed reduced FC between the PAG and the left primary sensorimotor cortex. No significant differences between groups were found in spinal cord macrostructure. These findings demonstrate that participants with different outcomes exhibit distinct preoperative patterns of brain reorganization, particularly in the PAG and its sensorimotor connectivity. These findings suggest that preoperative multimodal MRI may help identify participants unlikely to benefit from DREZ lesioning, potentially guiding surgical candidacy and personalized treatment planning.