Targeted modulation of thalamocortical and descending control networks in chronic shoulder pain: a longitudinal connectomics study

Background Central sensitization involves maladaptive plasticity in ascending nociceptive and descending modulatory pathways. This pilot study was designed with three integrated aims: (1) to characterize baseline thalamocortical and descending control network abnormalities in chronic shoulder pain (CSP) relative to healthy controls; (2) to examine whether these network features change following a standardized course of peripheral myofascial stimulation (PMS); and (3) to explore potential mechanistic pathways linking peripheral intervention to central network reconfiguration. While PMS has been reported anecdotally as effective for musculoskeletal pain, preliminary empirical evidence from randomized controlled trials remains limited, and its central neural mechanisms remain unclear. Methods Twelve patients with CSP underwent longitudinal resting-state fMRI before and after a 10-session PMS intervention. A matched healthy control cohort ( n = 18) provided cross-sectional baseline normative data for disease characterization only; no longitudinal data were collected from controls. High-resolution parcellation (HCP-MMP1.0) was used to quantify connectivity in a priori hypothesized networks. Statistical analysis employed a tiered approach combining whole-brain Network-Based Statistics ( N BS) and hypothesis-driven Region of Interest (ROI) analyses, rigorously controlled for site effects using ComBat harmonization. Results At baseline, patients exhibited trend-level reduced thalamo-somatosensory coupling (Cohen's d = 0.72, p = 0.054) compared to controls, which correlated with disease burden. Following treatment, we observed: (1) a downregulation of ACC–brainstem connectivity at the ROI level (Pre 0.017 ± 0.209, Post −0.149 ± 0.211, Δ = −0.166; Wilcoxon p = 0.012, d = −0.82), which did not survive Bonferroni correction across the eight a priori edges (corrected p = 0.098); and (2) patient-specific change in thalamo-somatosensory connectivity, which was associated with change in present pain intensity ( Δ PPI, ρ = −0.73). Control analyses in visual and limbic networks were null; this is compatible with, but does not confirm, anatomical restriction. Conclusions PMS is associated with the reconfiguration of specific bottom-up gating and top-down control circuits in CSP. While the absence of a sham control and the small sample size ( n = 12) limit causal inference and generalizability, the large effect sizes and high anatomical specificity suggest these are preliminary biological signals worthy of further investigation. These preliminary findings provide mechanistic targets for future adequately powered randomized controlled trials.