Central effects of short-term spinal cord stimulation in postherpetic neuralgia: a longitudinal fMRI and DTI study

Postherpetic neuralgia (PHN), a refractory neuropathic pain following herpes zoster reactivation, lacks clear central mechanisms for emerging therapies like short-term spinal cord stimulation (stSCS). This longitudinal study used multimodal neuroimaging to examine the effects of 14-day stSCS on brain function and white matter microstructure in PHN patients, and to identify neural correlates of clinical improvements.

In this longitudinal, single-arm, pre-post study, 17 PHN patients received 14 days of continuous stSCS. Clinical outcomes including pain intensity (Numeric Rating Scale, NRS), anxiety and depression (Hospital Anxiety and Depression Scale, HADS), and sleep quality (Pittsburgh Sleep Quality Index, PSQI), were assessed pre-stSCS and 3 days post-stSCS. Resting-state functional MRI (rs-fMRI) and Diffusion Tensor Imaging (DTI) data were acquired at both time points. Longitudinal changes in amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) were analyzed, alongside white matter integrity via TBSS and ROI analysis of key tracts.

Post-stSCS, significant improvements occurred in all clinical outcomes (Wilcoxon signed-rank, all p < 0.001). Neuroimaging showed no DTI microstructural changes but significant fALFF increases in regions including the dorsal striatum. Notably, right medial orbitofrontal cortex (mOFC) fALFF increases correlated with NRS reductions (Spearman's r = 0.71, FDR-corrected p = 0.036). Baseline cingulum integrity (lower FA, higher MD/RD) predicted greater striatal fALFF changes (r = ±0.75, FDR-corrected p < 0.02).

These findings suggest that stSCS's early clinical benefits in PHN are mediated by rapid functional reorganization rather than immediate microstructural changes. This reorganization appears prominent within fronto-striatal circuits: specifically, mOFC functional changes correlate with analgesia, while baseline cingulum integrity predicts subsequent striatal plasticity. This provides initial mechanistic insights into stSCS and suggest that baseline brain structure could be explored as a potential biomarker for treatment response, warranting validation in larger, controlled cohorts.