Dysmenorrhea is the most prevalent gynecological disorder in women of child-bearing age. Dysmenorrhea is associated with central sensitization and functional and structural changes in the brain. Our recent brain morphometry study disclosed that dysmenorrhea is associated with trait-related abnormal gray matter (GM) changes, even in the absence of menstrual pain, indicating that the adolescent brain is vulnerable to menstrual pain. Here we report rapid state-related brain morphological changes, ie, between pain and pain-free states, in dysmenorrhea. We used T1-weighted anatomic magnetic resonance imaging to investigate regional GM volume changes between menstruation and periovulatory phases in 32 dysmenorrhea subjects and 32 age- and menstrual cycle-matched asymptomatic controls. An optimized voxel-based morphometry analysis was conducted to disclose the possible state-related regional GM volume changes across different menstrual phases. A correlation analysis was also conducted between GM differences and the current menstrual pain experience in the dysmenorrhea group. Compared with the periovulatory phase, the dysmenorrhea subjects revealed greater hypertrophic GM changes than controls during the menstruation phase in regions involved in pain modulation, generation of the affective experience, and regulation of endocrine function, whereas atrophic GM changes were found in regions associated with pain transmission. Volume changes in regions involved in the regulation of endocrine function and pain transmission correlated with the menstrual pain experience scores. Our results demonstrated that short-lasting cyclic menstrual pain is associated not only with trait-related but also rapid state-related structural alterations in the brain. Considering the high prevalence rate of menstrual pain, these findings mandate a great demand to revisit dysmenorrhea with regard to its impact on the brain and other clinical pain conditions.

Primary dysmenorrhea (PDM) is the most prevalent gynecological problem. Many key brain systems are engaged in pain processing. In light of dynamic communication within and between systems (or networks) in shaping pain experience and behavior, the intra-regional functional connectivity (FC) in the hub regions of the systems may be altered and the functional interactions in terms of inter-regional FCs among the networks may be reorganized to cope with the repeated stress of menstrual pain in PDM. Forty-six otherwise healthy PDM subjects and 49 age-matched, healthy female control subjects were enrolled. Intra- and inter-regional FC were assessed using regional homogeneity (ReHo) and ReHo-seeded FC analyses, respectively. PDM women exhibited a trait-related ReHo reduction in the ventromedial prefrontal cortex, part of the default mode network (DMN), during the periovulatory phase. The trait-related hypoconnectivity of DMN-salience network and hyperconnectivity of DMN-executive control network across the menstrual cycle featured a dynamic transition from affective processing of pain salience to cognitive modulation. The altered DMN-sensorimotor network may be an ongoing representation of cumulative menstrual pain. The findings indicate that women with long-term PDM may develop adaptive neuroplasticity and functional reorganization with a network shift from affective processing of salience to the cognitive modulation of pain.

Primary dysmenorrhea (PDM), painful menstruation without organic causes, is the most prevalent gynecological problem in women of reproductive age. Dysmenorrhea later in life often co-occurs with many chronic functional pain disorders, and chronic functional pain disorders exhibit altered large-scale connectedness between distributed brain regions. It is unknown whether the young PDM females exhibit alterations in the global and local connectivity properties of brain functional networks. Fifty-seven otherwise healthy young PDM females and 62 age- and education-matched control females participated in the present resting-state functional magnetic resonance imaging study. We used graph theoretical network analysis to investigate the global and regional network metrics and modular structure of the resting-state brain functional networks in young PDM females. The functional network was constructed by the interregional functional connectivity among parcellated brain regions. The global and regional network metrics and modular structure of the resting-state brain functional networks were not altered in young PDM females at our detection threshold (medium to large effect size differences [Cohen’s d ≥ 0.52]). It is plausible that the absence of significant changes in the intrinsic functional brain architecture allows young PDM females to maintain normal psychosocial outcomes during the pain-free follicular phase.

ObjectiveRecent functional MRI (fMRI) studies show that brain activity, including the default mode network (DMN), can be modulated by acupuncture. Conventional means to enhance the neurophysiological ‘dose’ of acupuncture, including an increased number of needles and manual needle manipulation, are expected to enhance its physiological effects. The aim of this study was to compare the effects of both methods on brain activity.Methods58 healthy volunteers were randomly assigned into four groups that received single needle acupuncture (SNA, n=15) or transcutaneous electrical nerve stimulation (TENS, n=13) as active controls, or enhanced acupuncture by way of three needle acupuncture (TNA, n=17) or SNA plus manual stimulation (SNA+MS, n=13). Treatment-associated sensations were evaluated using a visual analogue scale. Central responses were recorded before, during, and after treatment at LI4 on the left hand using resting state fMRI.ResultsTNA and SNA+MS induced DMN-insula activity and extensive DMN activity compared to SNA, despite comparable levels of de qi sensation. The TNA and SNA+MS groups exhibited a delayed and enhanced modulation of the DMN, which was not observed followed SNA and TENS. Furthermore, TNA increased precuneus activity and increased the DMN-related activity of the cuneus and left insula, while SNA+MS increased activity in the right insula.ConclusionsThe results showed that conventional methods to enhance the acupuncture dose induce different DMN modulatory effects. TNA induces the most extensive DMN modulation, compared with other methods. Conventional methods of enhancing the acupuncture dose could potentially be applied as a means of modulating brain activity.

The aim of this study was to investigate the autonomic responses and central manifestations by peripheral FIR stimulation. Ten subjects (mean ± SD age 26.2 ± 3.52 years) received FIR stimulation at left median nerve territory for 40 min. Electrocardiograph was continuously recorded and heart rate variability (HRV) were analyzed. By using a 3 T-MRI scanner, three sessions of resting-state functional magnetic resonance images (fMRI) were acquired, namely, before (baseline-FIR), immediately after (IA-FIR) and 15 min after FIR was turned off (Post-FIR). The fractional amplitude of low-frequency (0.01-0.08 Hz) fluctuation (fALFF) of each session to evaluate the intensity of resting-brain activity in each session was analyzed. Our results showed that FIR stimulation induced significant HRV responses such as an increasing trend of nLF and LF/HF ratio, while FIR increased fALFF in right superior front gyrus, middle frontal gyrus and decreased the resting brain activity at fusiform gyrus, extrastriae cortex, inferior temporal gyrus and middle temporal gyrus, especially 15 min after FIR was turned off. We conclude that the central manifestation and the autonomic responses are prominent during and after FIR stimulation, which provide important mechanistic explanation on human disorder treated by such energy medicine.