Abstract
BACKGROUND: In clinical practice, the overall effect of a treatment includes specific and nonspecific components. Although the analgesic mechanism of specific acupuncture effect has been studied extensively, the understanding of neural basis about nonspecific placebo effect is insufficient. We aimed to reveal the neurological signatures associated with both specific effect and nonspecific effect of acupuncture in chronic pain using the functional magnetic resonance imaging (fMRI). METHODS: In this three-armed, randomized controlled trial, 90 patients with knee osteoarthritis (KOA) were divided into acupuncture group (AG), sham acupuncture group (SG), or waiting list group (WG), receiving 12 times of treatments during 4 weeks. NRS, WOMAC score, and fMRI data were collected before and after treatment. We assessed the amplitude of low frequency fluctuation (ALFF) and seed-based functional connectivity (FC) to investigate the brain functional bases of the nonspecific (SG vs. WG) and specific (AG vs. SG) effects of acupuncture. RESULTS: Acupuncture could significantly reduce NRS score in KOA patients (overall P < 0.001). Neurally, significant ALFF changes in left dorsolateral prefrontal cortex (DLPFC) were observed in the AG (vs. SG) and SG (vs. WG; Voxel P < 0.001, Cluster P < 0.001), respectively. And the decreased ALFF values of DLPFC had a positive correlation with the NRS score changes in the SG (spearman rho = 0.592, P = 0.002). Moreover, FC between DLPFC and thalamus was increased in the AG compared to SG. And compared to WG, there was a decreased FC between DLPFC and cerebellum in the SG. CONCLUSION: The spontaneous activity of the DLPFC was involved in both the specific and nonspecific acupuncture effects, whereas different DLPFC FCs related to the specific or nonspecific effects of acupuncture. Our findings contribute to the understanding about the neuroimaging evidence of the acupuncture effects. TRIAL REGISTRATION NUMBERS: Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR1900025799. This study was registered on 9th September 2019.