Objective:

2

To elucidate how spinal manipulative therapy (SMT) exerts its analgesic effects through regulating brain function in lumbar disc herniation (LDH) patients by utilizing resting-state functional magnetic resonance imaging (rs-fMRI).

Methods:

2

From September 2021 to September 2023

we enrolled LDH patients (LDH group

n

=31) and age- and sex-matched healthy controls (HCs

n

=28). LDH group underwent rs-fMRI at 2 distinct time points (TPs): prior to the initiation of SMT (TP1) and subsequent to the completion of the SMT sessions (TP2). SMT was administered once every other day for 30 min per session

totally 14 treatment sessions over a span of 4 weeks. HCs did not receive SMT treatment and underwent only one fMRI scan. Additionally

participants in LDH group completed clinical questionnaires on pain using the Visual Analog Scale (VAS) and the Japanese Orthopedic Association (JOA) score

whereas HCs did not undergo clinical scale assessments. The effects on the brain were jointly characterized using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). Correlation analyses were conducted between specific brain regions and clinical scales.

Results:

2

Following SMT treatment

pain symptoms in LDH patients were notably alleviated and accompanied by evident activation of effects in the brain. In comparison to TP1

TP2 exhibited the most significant increase in ALFF values for Temporal_Sup_R and the most notable decrease in ALFF values for Paracentral_Lobule_L (voxelwise

P

<

0.005; clusters

>

30; FDR correction). Additionally

the most substantial enhancement in ReHo values was observed for the Cuneus_R

while the most prominent reduction was noted for the Olfactory_R (voxelwise

P

<

0.005; clusters

>

30; FDR correction). Moreover

a comparative analysis revealed that

in contrast to HCs

LDH patients at TP1 exhibited the most significant increase in ALFF values for Temporal_Pole_Sup_L and the most notable decrease in ALFF values for Frontal_Mid_L (voxelwise

P

<

0.005; clusters

>

30; FDR correction). Furthermore

the most significant enhancement in ReHo values was observed for Postcentral_L

while the most prominent reduction was identified for ParaHippocampal_L (voxelwise

P

<

0.005; clusters

>

30; FDR correction). Notably

correlation analysis with clinical scales revealed a robust positive correlation between the Cuneus_R score and the rate of change in the VAS score (

r

=0.9333

P

<

0.0001).

Conclusions:

2

Long-term chronic lower back pain in patients with LDH manifests significant activation of the "AUN-DMN-S1-SAN" neural circuitry. The visual network

represented by the Cuneus_R

is highly likely to be a key brain network in which the analgesic efficacy of SMT becomes effective in treating LDH patients. (Trial registration No. NCT 06277739)