Modulatory Effects of Actual and Imagined Acupuncture on the Functional Connectivity of the Periaqueductal Gray and Ventral Tegmental Area

Abstract

Objective: Both acupuncture and guided imagery hold promise for treating pain. The mechanisms underlying these alternative interventions remain unclear. The reported study aimed to comparatively investigate the modulation effect of actual and imagined acupuncture on the functional connectivity of descending pain modulation system and reward network. Methods: Twenty-four healthy participants (mean [standard error], 25.21 [0.77] years of age; 66.67% female) completed a crossover study that included five sessions, a training session and four intervention sessions administered in randomized order. We investigated the modulation effect of real acupuncture, sham acupuncture, video-guided acupuncture imagery treatment (VGAIT) and VGAIT control on the resting-state functional connectivity (rsFC) of periaqueductal gray (PAG) and ventral tegmental area (VTA). These are key regions of the descending pain modulatory system and dopaminergic reward system, respectively. Results: Compared with sham acupuncture, real acupuncture produced decreased PAG-precuneus (Pcu) rsFC and increased VTAamygdala/hippocampus rsFC. Heat pain threshold changes applied on the contralateral forearm were significantly associated with the decreased PAG-Pcu (r = 0.49, p = .016) and increased VTA-hippocampus rsFC (r = −0.77, p < .001). Compared with VGAIT control, VGAIT produced decreased PAG-paracentral lobule/posterior cingulate cortex/Pcu, middle cingulate cortex (MCC), and medial prefrontal cortex rsFC, and decreased VTA-caudate and MCC rsFC. Direct comparison between real acupuncture and VGAIT showed that VGAIT decreased rsFC in PAG-paracentral lobule/MCC, VTA-caudate/anterior cingulate cortex/nucleus accumbens, and VTA-MCC. Conclusions: Results suggest that both actual and imagined acupuncture can modulate key regions in the descending pain modulatory system and reward networks, but through different pathways. Identification of different pain relief mechanisms may facilitate the development of new pain management methods.

Multidimensional Pain Modulation by Acupuncture Analgesia: The Reward Effect of Acupuncture on Pain Relief

“…Acupuncture, as a technique of peripheral nerve regulation, has paid significant attention to the role of the central circuit [ 16 ]. Previous studies have pointed out that acupuncture analgesia can activate the brain reward circuit [ 16 , 65 – 67 ]. A previous study [ 68 ] has reported that the analgesic effect of acupuncture affects the “self-evaluation” of the human body and activates the brain reward system, with the activation of the brain striatal system being an essential mechanism for acupuncture to produce pleasure [ 69 ].…”

Modulation effects of different treatments on periaqueductal gray resting state functional connectivity in knee osteoarthritis knee pain patients

“…A priori vlPAG seed with the following peak coordinates: 4, −26, −14, and a 3 mm radius was utilized. This seed was already utilized in earlier investigations 40,43,50,51,69 . There are four reasons why this seed was chosen: (1) the study found that an increase in the degree of heat pain resulted in a significant increase in fMRI signal in the same region, 70 (2) its site in the vlPAG was perceived as essential for opioid antinociception, 71,72 (3) celecoxib was discovered to cross the blood–brain barrier (BBB) with the maximum rate of flow accumulated in the midbrain (within PAG), 23–25 and (4) prior research declared that the seed was functionally linked to descending modulatory pain sites at the resting status in healthy control subjects, and a significant variation was observed between healthy subjects and chronic pain subjects 40,51,56 .…”

“…This seed was already utilized in earlier investigations. 40 , 43 , 50 , 51 , 69 There are four reasons why this seed was chosen: (1) the study found that an increase in the degree of heat pain resulted in a significant increase in fMRI signal in the same region, 70 (2) its site in the vlPAG was perceived as essential for opioid antinociception, 71 , 72 (3) celecoxib was discovered to cross the blood–brain barrier (BBB) with the maximum rate of flow accumulated in the midbrain (within PAG), 23 , 24 , 25 and (4) prior research declared that the seed was functionally linked to descending modulatory pain sites at the resting status in healthy control subjects, and a significant variation was observed between healthy subjects and chronic pain subjects. 40 , 51 , 56 Due to the proximity of the vlPAG seed region to a ventricle with a high pulsatile impact, a seed from a neighboring ventricular aqueduct (peak coordinates: 0, −34, −12, with a 3 mm radius) and seeds from the fourth ventricle (peak coordinates: ±4, 8, 12) 40 were selected as controls.…”

“…The resting‐state functional magnetic resonance imaging (fMRI) technique allows for the identification of correlations between remote brain regions (resting‐state functional connectivity, rs‐FC) through their highly correlated low‐frequency spontaneous fluctuations non‐invasively 42 . Recently, many research groups have applied rs‐FC to evaluate the DPMS in humans 40,43,44 . The periaqueductal gray (PAG) is a mesencephalic brain structure between the third and fourth ventricles 45 .…”

“… 42 Recently, many research groups have applied rs‐FC to evaluate the DPMS in humans. 40 , 43 , 44 The periaqueductal gray (PAG) is a mesencephalic brain structure between the third and fourth ventricles. 45 The PAG has several sub‐regions, of which ventrolateral PAG (vlPAG) is the key node of the DPMS.…”