Imaging the functional connectivity of the Periaqueductal Gray during genuine and sham electroacupuncture treatment

Department of Psychiatry, Massachusetts General Hospital, Charlestown, USA.
Molecular Pain (Impact Factor: 3.65). 11/2010; 6(1). DOI: 10.1186/1744-8069-6-80
Source: DOAJ



Electroacupuncture (EA) is currently one of the most popular acupuncture modalities. However, the continuous stimulation characteristic of EA treatment presents challenges to the use of conventional functional Magnetic Resonance Imaging (fMRI) approaches for the investigation of neural mechanisms mediating treatment response because of the requirement for brief and intermittent stimuli in event related or block designed task paradigms. A relatively new analysis method, functional connectivity fMRI (fcMRI), has great potential for studying continuous treatment modalities such as EA. In a previous study, we found that, compared with sham acupuncture, EA can significantly reduce Periaqueductal Gray (PAG) activity when subsequently evoked by experimental pain. Given the PAG's important role in mediating acupuncture analgesia, in this study we investigated functional connectivity with the area of the PAG we previously identified and how that connectivity was affected by genuine and sham EA.

Forty-eight subjects, who were randomly assigned to receive either genuine or sham EA paired with either a high or low expectancy manipulation, completed the study. Direct comparison of each treatment mode's functional connectivity revealed: significantly greater connectivity between the PAG, left posterior cingulate cortex (PCC), and precuneus for the contrast of genuine minus sham; significantly greater connectivity between the PAG and right anterior insula for the contrast of sham minus genuine; no significant differences in connectivity between different contrasts of the two expectancy levels.

Our findings indicate the intrinsic functional connectivity changes among key brain regions in the pain matrix and default mode network during genuine EA compared with sham EA. We speculate that continuous genuine EA stimulation can modify the coupling of spontaneous activity in brain regions that play a role in modulating pain perception.

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    • "We chose to create this functionally rather than an anatomically defined mask, as PAG is involved in a number of functions not related to pain. This functionally defined mask covers the coordinates reported for pain, acupuncture and placebo, as identified in a recent meta-analysis (Linnman et al., 2012b), as well as a number of other studies (Kucyi et al., 2013; Zyloney et al., 2010). Connectivity of PAG seed with the anatomically defined bilateral Hpc (combined volume 38,189 mm 3 ) and MFC (volume 30,833 mm 3 ) (based on the Harvard–Oxford cortical and subcortical structural atlases, implemented in CONN) was examined. "
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    ABSTRACT: Acupuncture, an ancient East Asian therapy, is aimed at rectifying the imbalance within the body caused by disease. Studies evaluating the efficacy of acupuncture with neuroimaging tend to concentrate on brain regions within the pain matrix, associated with acute pain. We, however, focused on the effect of repeated acupuncture treatment specifically on brain regions known to support functions dysregulated in chronic pain disorders. Transition to chronic pain is associated with increased attention to pain, emotional rumination, nociceptive memory and avoidance learning, resulting in brain connectivity changes, specifically affecting the periaqueductal gray (PAG), medial frontal cortex (MFC) and bilateral hippocampus (Hpc). We demonstrate that the PAG-MFC and PAG-Hpc connectivity in patients with chronic pain due to knee osteoarthritis indeed correlates with clinical severity scores and further show that verum acupuncture-induced improvement in pain scores (compared to sham) is related to the modulation of PAG-MFC and PAG-Hpc connectivity in the predicted direction. This study shows that repeated verum acupuncture might act by restoring the balance in the connectivity of the key pain brain regions, altering pain-related attention and memory.
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    • "Baliki et al. revealed that the disruption of DMN might underlie the cognitive and behavioral impairments accompanying chronic pain (Baliki et al., 2008). A recent study revealed more connectivity between the periaqueductal gray (PAG) and the PCC during a 25 min EA as compared to sham EA (Zyloney et al., 2010), suggesting that the DMN may play a central role in acupuncture analgesia. Thus, it may give us an insight into the mechanisms of acupuncture's clinical effects. "

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    • "As a unique treatment modality, studies have shown that acupuncture may produce an analgesic effect through the endogenous descending pain modulatory system141516. Brain imaging studies have also shown that acupuncture needle stimulation1718192021 can evoke widespread brain activity changes and modulate the functional connectivity (FC) of the pain processing network2223242526272829, which opens a new window to understand the central mechanism of acupuncture treatment. "
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