Background/Objectives: Persistent spinal pain, including chronic low back pain (CLBP), chronic neck pain, and whiplash-associated disorders (WAD), is a highly prevalent musculoskeletal condition. The recent literature emphasizes a biopsychosocial framework, acknowledging that altered pain processing, psychological impairments, and autonomic nervous system dysfunction are associated with chronic pain. However, the concurrent within-sample relationships between these domains remain poorly understood and inconsistently reported. To systematically evaluate the associations among physiological autonomic measures, validated psychosocial scales, and pressure algometry in adults with persistent spinal pain. Methods: A systematic search was conducted in accordance with PRISMA guidelines. A systematic search was conducted across four electronic databases (PubMed, Web of Science, Scopus, and CINAHL) for studies evaluating all three domains within the same cohort. The search was restricted to peer-reviewed articles published in English and Spanish. Two independent blinded reviewers screened and selected the studies. Eligible studies evaluated within-sample relationships across three domains: autonomic indices (e.g., heart rate variability (HRV) and blood pressure (BP)), psychosocial factors (e.g., kinesiophobia and pain catastrophizing), and quantitative sensory testing (QST) (e.g., pressure pain threshold (PPTs)). Quality assessment was performed using the National Institutes of Health (NIH) tools. Due to significant methodological heterogeneity, the data were synthesized narratively. Results: Six studies fulfilled the eligibility criteria. The narrative synthesis revealed a preliminary pattern showing that objective functional outcomes and experimental pain processing tend to show closer associations with autonomic proxies (such as heart rate variability), whereas subjective clinical outcomes (such as perceived disability) are more consistently linked to psychosocial factors (such as kinesiophobia and catastrophizing). Conclusions: These preliminary findings suggest potentially distinct domain-specific associations rather than a uniform pathophysiological mechanism. Future specialized research and research-informed practice should incorporate multimodal assessments to better characterize individual patient profiles.

Introduction: Persistent Spinal Pain Syndrome Type 2 (PSPS-T2) is associated with changes in the brain’s pain processing. This is often due to problems with the body’s natural way of handling the pain management system. Exercise therapy, such as motor control and spinal stabilization, can help reduce pain and disability. However, exercise alone may not be sufficient. Approaches that consider both body mechanics and brain function are gaining popularity. Since brain changes play a role in muscle and bone problems, noninvasive brain stimulation (NIBS) is considered a helpful adjunctive treatment. Studies have shown that NIBS may help people with spinal pain and mood disorders. The aim of this study is to assess the impact of combining tDCS targeting the dorsolateral prefrontal cortex with spinal motor control exercises in patients diagnosed with PSPS-T2. This investigation is based on the hypothesis that such a combined intervention could result in a more significant reduction in disability. Methods/Materials: This randomized controlled trial (RCT) is structured as a double-blind, comparative, longitudinal design in accordance with the CONSORT guidelines. This RCT has been registered at ClinicalTrials.gov (NCT06969456). Forty-two participants diagnosed with PSPS-T2 will be randomized in a 1:1 ratio into two groups: tDCS + rehabilitation (E_tDCS) or sham tDCS + rehabilitation (E_SHAM). The intervention will use tDCS to deliver low-intensity direct current to modulate cortical excitability. The intervention will consist of 24 supervised sessions (2 per week, 60 min each) over 12 weeks. Neuromodulation and exercise protocols will be adapted to the intervention phases based on previous research. The sample size has been calculated using GPower^®, assuming an effect size of 0.81, α = 0.05, power = 0.95, and a 40% dropout rate. Data will be collected from October 2025 to January 2027. Impact Statement: This study integrates neurophysiological modulation via tDCS with targeted exercise therapy, presenting an innovative approach to enhance pain modulation, functional recovery, and cortical reorganization in patients with PSPT-2. This approach has the potential to inform future evidence-based strategies for neurorehabilitation and pain management.