Abstract
The aims of this study were to 1) compare resting state functional connectivity (rs-fc) of the periaqueductal gray (PAG), a key region in the descending pain modulatory system (DPMS) between migraine without aura (MwoA) patients and healthy controls (HC), and 2) investigate how an effective treatment can influence the PAG rs-fc in MwoA patients. One hundred MwoA patients and forty-six matched HC were recruited. Patients were randomized to verum acupuncture, sham acupuncture, and waiting list groups. Resting state fMRI data were collected and seed based functional connectivity analysis was applied. Compared with HC, MwoA patients showed reduced rs-fc between the PAG and rostral anterior cingulate cortex/medial prefrontal cortex (rACC/mPFC), key regions in the DPMS and other pain related brain regions. The reduced rs-fc between the PAG and rACC/mPFC was associated with increased migraine headache intensity at the baseline. After treatments, rs-fc between the PAG and the rACC in MwoA patients significantly increased. The changes of rs-fc among the PAG, rACC and ventral striatum were significantly associated with headache intensity improvement. Impairment of the DPMS is involved in the neural pathophysiology of migraines. Impaired DPMS in migraine patients can be normalized after effective treatment.
Highlights
The aims of this study were to 1) compare resting state functional connectivity of the periaqueductal gray (PAG), a key region in the descending pain modulatory system (DPMS) between migraine without aura (MwoA) patients and healthy controls (HC), and 2) investigate how an effective treatment can influence the PAG rs-fc in MwoA patients
The rationales for choosing this seed are: 1) we found that increased levels of heat pain can evoke a significant fMRI signal increase in this region26, 2) it is located within the ventrolateral periaqueductal gray (vlPAG), which is believed to be important for opioid antinociception[27], and 3) in previous rs-fc studies, we found the seed is functionally connected to the key regions of descending pain modulation system (DPMS) during resting in healthy subjects[12], and showed significant difference between healthy subjects and chronic low back pain patients[13]
150 patients were screened and 100 patients were recruited for this study. 46 age and sex-matched healthy controls were recruited in this study, 4 HCs were excluded due to excessive head movements. 88 patients participated in first fMRI scan, 81 patients participated in the second fMRI scan. 7 patients did not participate in the second fMRI scan, due to scheduling conflicts (2 in VA1, 2 in VA2, 1 in VA3, and 2 in sham acupuncture group (SA) groups)
Summary
The aims of this study were to 1) compare resting state functional connectivity (rs-fc) of the periaqueductal gray (PAG), a key region in the descending pain modulatory system (DPMS) between migraine without aura (MwoA) patients and healthy controls (HC), and 2) investigate how an effective treatment can influence the PAG rs-fc in MwoA patients. Compared with HC, MwoA patients showed reduced rs-fc between the PAG and rostral anterior cingulate cortex/medial prefrontal cortex (rACC/mPFC), key regions in the DPMS and other pain related brain regions. We investigated the rs-fc of PAG, a key region in the DPMS, and found significant rs-fc among the PAG, the central region of the DPMS, the rACC, the rostroventral medulla (RVM), the orbital prefrontal cortex and other brain regions[12] These findings demonstrate the feasibility of using rs-fc to non-invasively investigate the DPMS in humans. We hypothesize that 1) migraine is associated with dysfunction of DPMS as indicated by rs-fc changes between the PAG and key regions of DPMS; 2) an effective treatment can normalize the impaired rs-fc of DPMS
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