Cheng-Hao Tu, Ph.D.

Assistant Research Fellow, Department of Medical Research, China Medical University Hospital, Taiwan

Primary dysmenorrhea (PDM) is the most encountered gynecological problem for women in the reproductive age. We previously reported the altered functional connectivity (FC) between periaqueductal gray matter (PAG) and other pain-related brain regions in PDM, indicated the maladaptation of the descending pain modulation system in PDM. Clinically, acupuncture has been suggested as an effective treatment of PDM. Thus, in the present study we hypothesized that acupuncture intervention in PDM may associated with the resilience of maladapted FC in descending pain modulation system in terms of FC between PAG and other pain-related brain areas.

Eighteen right-handed young PDMs were participated in this randomized, single-blinded, placebo-controlled study. Each subject received an 8-week acupuncture intervention session (20-min verum or non-penetrated sham acupuncture on bilateral sanyinjiao [SP6], twice per week). Two hundred resting-state functional magnetic resonance imaging (rfMRI) scans and an anatomical T1 image were taken using 3T Signa HDx scanner during follicular phase (day 5-12 of menstrual cycle) at week 0, 4, and 8. The menstrual pain experience, anxiety level, and depression level in each subject were evaluated prior to each scan using McGill pain questionnaire, Spielberger state-trait anxiety inventory, and Beck depression inventory, respectively. The blood sample also has been collected after each scan to measure the hormone level of estradiol, progesterone, and testosterone. Two-way ANOVA with repeated-measured has been conducted for psychological and hormonal data. Significance was considered if p<0.05. For imaging data, the rfMRI has been preprocessed and then used to generated the FC maps between PAG and other brain regions. Two-way mixed-model ANOVA has been conducted for imaging statistics. A more liberal significant threshold (uncorrected p<0.005 at voxel-level, with the cluster size >50) was applied to the analysis.

Twelve PDMs received verum acupuncture and 6 PDMs received sham acupuncture. No significant difference has been found between groups in their demographic data and recalled overall menstrual pain experience. After the 8-weeks intervention session, significantly reduced total and sensory dimension of menstrual pain experience has been found across all subjects. No significant difference has been found in all psychological and hormonal data, expect testosterone level. The increased FC has been revealed between PAG and right ventrolateral prefrontal cortex (vlPFC), bilateral cuneus, bilateral thalamus, midbrain, and cerebellum, whereas decreased FC has been revealed between PAG and left primary somatosensory cortex, left primary motor cortex, and right superior temporal gyrus in verum acupuncture group. In sham acupuncture group, increased FC has been revealed in left precuneus and left posterior cingulate cortex (PCC), whereas decreased FC has been revealed in right anterior cingulate cortex and bilateral posterior parietal cortex (PPC).

In summary, altered FC of pain modulation system in PDMs may reversed by the verum but not sham acupuncture intervention. Furthermore, the dissimilar pattern of the resilience FC maps after the verum and sham acupuncture indicated that the relief of menstrual pain in both groups may underpinned by different brain mechanisms. These results may provide new evidence to the argument whether acupuncture intervention will induce therapeutic neurophysiological alterations or just benefit from placebo effect.