Acupuncture Treatment Modulates the Connectivity of Key Regions of the Descending Pain Modulation and Reward Systems in Patients with Chronic Low Back Pain

Abstract

Chronic low back pain (cLBP) is a common disorder with unsatisfactory treatment options. Acupuncture has emerged as a promising method for treating cLBP. However, the mechanism underlying acupuncture remains unclear. In this study, we investigated the modulation effects of acupuncture on resting state functional connectivity (rsFC) of the periaqueductal gray (PAG) and ventral tegmental area (VTA) in patients with cLBP. Seventy-nine cLBP patients were recruited and assigned to four weeks of real or sham acupuncture. Resting state functional magnetic resonance imaging data were collected before the first and after the last treatment. Fifty patients completed the study. We found remission of pain bothersomeness in all treatment groups after four weeks, with greater pain relief after real acupuncture compared to sham acupuncture. We also found that real acupuncture can increase VTA/PAG rsFC with the amygdala, and the increased rsFC was associated with decreased pain bothersomeness scores. Baseline PAG-amygdala rsFC could predict four-week treatment response. Our results suggest that acupuncture may simultaneously modulate the rsFC of key regions in the descending pain modulation (PAG) and reward systems (VTA), and the amygdala may be a key node linking the two systems to produce antinociceptive effects. Our findings highlight the potential of acupuncture for chronic low back pain management.

Keywords: PAG; VTA; acupuncture; chronic low back pain; descending pain modulation system; functional connectivity; reward network.

Figure 1

Procedures and data used for the study.

Figure 2

(A) The location of the selected PAG seed (seeds marked in red). (B) Compared to sham group, real group had significantly higher rsFC with the RVM and left/right amygdala and lower rsFC with the right Pcu/SPL and middle insula. (C) The location of the selected VTA seed. (D) Compared to sham group, real group had significantly higher rsFC with the bilateral ACC/mPFC and left amygdala and lower rsFC with the SPL/Pcu and right IN. Abbreviations: PAG, periaqueductal gray; rsFC, resting-state functional connectivity; RVM, rostroventromedial medulla; VTA, ventral tegmental area; Pcu/SPL, precuneus/superior parietal lobe; IN, insula; AMY, amygdala; ACC/mPFC, anterior cingulate cortex/medial frontal cortex.

Figure 3

(A) Brain regions showed overlap at the left amygdala when using both the VTA and PAG as seeds (red, PAG seed; green, VTA seed; yellow, overlapping region). (B) Scatter plots indicate the correlation between change in pain bothersomeness score and change in mean z value of VTA-left amygdala rsFC across all cLBP subjects adjusted for age and gender. (C) Scatter plots indicate the correlation between change in pain bothersomeness score and mean z values change in PAG-left amygdala rsFC across all cLBP subjects adjusted for age and gender. (D) Predicting the effects of acupuncture on pain in cLBP patients with the left amygdala cluster. Correlation between prediction value (rsFC value of PAG-amygdala at baseline) and pain bothersomeness score change across all cLBP patients adjusted for age and gender. Abbreviations: VTA, ventral tegmental area; PAG, periaqueductal gray; rsFC, resting-state functional connectivity; cLBP, chronic low back pain.

Figure 4

Scatter plots indicate the correlation between change in pain bothersomeness score and corresponding change in mean z value of VTA-bilateral ACC/mPFC rsFC across all cLBP subjects adjusted for age and gender. Abbreviations: VTA, ventral tegmental area; ACC/mPFC, anterior cingulate cortex/medial prefrontal cortex; rsFC, resting-state functional connectivity; cLBP, chronic low back pain.