This is a single-center, randomized, double-blind, sham-controlled trial evaluating dual-carrier-frequency transcranial alternating current stimulation targeting the hippocampus in 60 patients with chronic non-specific low back pain. Participants will be randomized into four groups: active stimulation, active stimulation with iTBS, superficial stimulation control, and sham control. All groups will receive standard rehabilitation. The intervention is 20 minutes per session, 5 sessions weekly for 2 weeks (10 sessions total).
The primary objective is to assess improvements in pain intensity (VAS) and emotional symptoms (anxiety, depression) at week 2. Exploratory objectives include examining functional connectivity changes between the hippocampus and prefrontal/sensory cortices using fMRI, MEG, and fNIRS, and correlating these with clinical improvements.
Outcomes include VAS (primary), McGill Pain Questionnaire, HAMA, HAMD, ODI, CSI, PSQI, and objective measures (brain imaging, EEG, EMG). Assessments occur at baseline (T0), post-first stimulation (T1), mid-treatment (T2), treatment end (T3), and 2-week follow-up (T4).
Linear mixed-effects models will be used for analysis with multiple comparison correction. This study aims to provide evidence for hippocampal-targeted neuromodulation in chronic non-specific low back pain.
Age between 18 and 80 years;
Meets the diagnostic criteria for non-specific low back pain as specified in the Chinese Clinical Guidelines for the Diagnosis and Treatment of Non-specific Low Back Pain (2022) ;
Diagnosed with chronic non-specific low back pain within the past 3 months, or pain located between T12 and the gluteal fold for at least half of the days within the past 6 months;
VAS score ≥ 3 (Visual Analogue Scale, 0-10);
Clear etiology of specific low back pain, such as vertebral fracture, severe spinal cord/nerve root compression symptoms (progressive neurological deficit), spinal infection, tumor, ankylosing spondylitis, etc.;
Prior major lumbar surgery or implants (e.g., internal fixation, spinal cord stimulation devices, etc.), or recent (within 3 months) invasive analgesic treatments such as nerve blocks or radiofrequency ablation;
Contraindications to MEG or MRI, including the presence of ferromagnetic metal implants in the body (e.g., cardiac pacemakers, hearing aids, carotid artery stents, etc.), claustrophobia that precludes MEG examination, or failed MEG acquisition;
History of severe cardiovascular disease, epilepsy, or other conditions that contraindicate electrical stimulation;
Parallel
Dual-carrier-frequency transcranial alternating current stimulation
DeviceDual-carrier-frequency transcranial alternating current stimulation is based on the interference principle. Two pairs of carrier-frequency alternating currents with slightly different frequencies are applied to the scalp. After intracranial superposition, the nonlinear response of biological tissues generates a low-frequency envelope-modulated electric field in deep brain regions. This interference electric field oscillates periodically at the difference between the two carrier frequencies, enabling entrainment and modulation of neuronal rhythms in deep structures. This distinguishes it from conventional transcranial electrical stimulation, in which electric field intensity decays exponentially with depth, predominantly affecting superficial cortical layers and having limited efficacy in modulating deep nuclei. In terms of safety, this technique is a non-invasive stimulation method. Adverse effects are limited to mild tingling or itching at the electrode contact sites, indicating favo
Transcranial electrical stimulation (tES)
DeviceCortical electrical stimulation is a neuromodulation technique in which electrodes are placed on the surface of the cerebral cortex or over the dura mater to deliver weak electrical currents for direct modulation of local neuronal electrical activity. By either exciting or inhibiting neuronal firing in specific cortical regions, it can regulate functional brain networks and is commonly used in studies on brain function mapping, neurorehabilitation, and pain modulation.
Visual Analogue Scale (VAS)
A 100-mm visual analogue scale is used, with "0" indicating no pain and "10" indicating the worst possible pain; the subject marks the current pain level on the scale, and the distance (mm) from the left end is measured as the VAS score
Ultrasound
A high-frequency linear array ultrasound probe (≥10 MHz) is placed over the erector spinae and multifidus muscles; cross-sectional and longitudinal gray-scale images are acquired in standardized positions, and muscle thickness, cross-sectional area, and echo intensity are measured using image analysis software to assess morphological and structural changes
Motion Sensors
Inertial measurement unit (IMU) sensors integrating tri-axial accelerometers, gyroscopes, and magnetometers are attached to the subject's lumbar region and bilateral lower limbs; continuous data on acceleration, angular velocity, and orientation are collected during standardized walking and trunk movement tasks, and gait parameters, trunk range of motion, and symmetry indices are calculated using dedicated algorithms
Central Sensitization Inventory (CSI)
A 25-item self-administered questionnaire is used, with each item scored from 0 to 4 (never to always); the total score ranges from 0 to 100, with higher scores indicating a higher degree of central sensitization
Magnetoencephalography (MEG)
A whole-head magnetoencephalography system is used to record spontaneous brain magnetic signals in a shielded room during the resting state; source localization algorithms are applied to reconstruct the magnetic signals from the scalp to the intracerebral source space, and spectral power and functional connectivity of the hippocampus and pain-related brain regions are assessed
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