Brain Connectomic Mechanisms of Spinal Manipulative Therapy on LDH Analgesia Based on Multimodal MRI

This is a single-center, prospective, randomized, participant- and outcome-assessor-masked, sham-controlled study with a matched healthy control cohort. Eighty-four participants with lumbar disc herniation will be randomly allocated 1:1 to active lever positioning manipulation or sham lever positioning manipulation using a computer-generated block randomization sequence prepared by an independent statistician. Allocation will be concealed in sequentially numbered, opaque, sealed envelopes. Forty-two age- and sex-matched healthy controls will complete baseline clinical and MRI assessments only.

Active and sham treatments will be delivered three times weekly for 12 weeks, with approximately 20 minutes per session. The sham procedure will reproduce the treatment setting, participant position, preparatory procedures, and practitioner contact but will omit the rapid lever-pulling maneuver. Analgesics, neurotrophic drugs, sedatives, spinal manipulation, acupuncture, traction, and other therapies that could affect pain or MRI outcomes will be prohibited during the treatment period.

Participants with LDH will be assessed at baseline before randomization, immediately after the first treatment session, at week 6, and at week 12. The primary outcome is change in pain intensity measured by the Visual Analog Scale from baseline to week 12. Secondary clinical outcomes include lumbar function measured by the Japanese Orthopaedic Association score and disability measured by the Oswestry Disability Index. Multimodal MRI will be used to evaluate longitudinal changes in functional network topology, white-matter structural connectivity, and structure-function coupling. Exploratory analyses will examine gray-matter covariance and associations between clinical improvement and imaging changes. Safety will be assessed through adverse-event monitoring and vital-sign checks at each treatment session.

Inclusion criteria

Patients with lumbar disc herniation (LDH):

• Diagnosis of LDH based on clinical symptoms, physical examination findings, and lumbar imaging consistent with neurological localization; central, paracentral, far-lateral, foraminal, or subarticular lumbar disc protrusion.
• Aged 18-65 years, of either sex, and right-handed.
• In the non-acute phase of LDH, with symptom duration of more than 2 weeks.
• Visual Analog Scale (VAS) score greater than 4 and Japanese Orthopaedic Association (JOA) score less than 15.
• No use of analgesics, neurotrophic drugs, or sedatives within 1 month before enrollment.
• No systematic treatment, spinal manipulation, or other physical therapies within 1 month before enrollment.
• Able to understand the study procedures and complete clinical assessments and MRI scans.
• Provides written informed consent.

Healthy controls:

• Aged 18-65 years, of either sex, and right-handed.
• No history of LDH or chronic low back pain.
• No current pain condition requiring treatment.
• No neurological or psychiatric disorders.
• No known structural brain abnormalities.
• No MRI contraindications.
• Able to complete clinical assessments and MRI scans.
• Provides written informed consent.

Exclusion criteria

Patients with LDH:

• Low back pain or sciatica caused by conditions other than LDH.
• Lumbar spondylolisthesis, lumbar tumor, spinal tuberculosis, severe osteoporosis, or localized lumbar skin lesions that may interfere with treatment.
• Severe cardiovascular, cerebrovascular, hepatic, renal, hematopoietic, neurological, or psychiatric disease.
• History of severe head trauma, loss of consciousness, or known structural brain abnormality.
• Impaired consciousness, severe visual or hearing impairment, speech disorder, or inability to complete clinical assessments.
• Non-MRI-compatible metal implants, implanted electronic devices, cardiac pacemakers, severe claustrophobia, or inability to tolerate MRI scanning.
• Asymptomatic LDH.
• Pregnancy, lactation, or planned pregnancy during the study period.
• Participation in another clinical trial within the previous 3 months.
• Any condition judged by the investigators to make the patient unsuitable for participation.

Healthy controls:

• Any condition that may affect eligibility, MRI safety, or data quality.