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Pain empathy, defined as the ability of one person to understand another person's pain, shows large individual variations. The anterior insula is the core region of the pain empathy network. However, the relationship between white matter (WM) properties of the fiber tracts connecting the anterior insula with other cortical regions and an individual's ability to modulate pain empathy remains largely unclear. In this study, we outline an automatic seed-based fiber streamline (sFS) analysis method and multivariate pattern analysis (MVPA) to predict the levels of pain empathy in healthy women and women with primary dysmenorrhoea (PDM). Using the sFS method, the anterior insula-based fiber tract network was divided into five fiber cluster groups. In healthy women, interindividual differences in pain empathy were predicted only by the WM properties of the five fiber cluster groups, suggesting that interindividual differences in pain empathy may rely on the connectivity of the anterior insula-based fiber tract network. In women with PDM, pain empathy could be predicted by a single cluster group. The mean WM properties along the anterior insular-rostroventral area of the inferior parietal lobule further mediated the effect of pain on empathy in patients with PDM. Our results suggest that chronic periodic pain may lead to maladaptive plastic changes, which could further impair empathy by making women with PDM feel more pain when they see other people experiencing pain. Our study also addresses an important gap in the analysis of the microstructural characteristics of seed-based fiber tract network., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Primary dysmenorrhea (PDM) is a cyclic menstrual pain in the absence of pelvic anomalies, and women with PDM have an increased sensitivity to pain than the internal and external areas associated with menstrual pain. However, the brain abnormality in the ascending pain pathways in dysmenorrhea remains largely unclear. As the thalamus plays a significant role in transmission of nociceptive input, we examined whether white matter microstructure of the thalamus-related fiber tracts obtained by DTI in women with PDM (n = 47) differs from healthy controls. A novel tractography atlas-based analysis method that detects tract integrity and altered microstructural properties along selected fibers was employed. The fiber bundles of interest contained the thalamus- primary somatosensory cortex (SI), thalamus- dorsal anterior cingulate cortex (dACC)/supplementary motor area (SMA), thalamus-insula, and thalamus-ACC. As compared with controls, abnormal white matter microstructures were found along the thalamus-related white matter fiber tracts. Additionally, the intensity of menstrual pain was significantly associated with diffusion measures of thalamus-SI fiber connections. Our study suggested that the thalamus-related pain processing pathways had altered white matter integrity that persisted beyond the time of menstruation, and the white matter microstructure of the thalamus-SI pathways was closely related to menstrual pain in the intensity by women with PDM., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Abstract: Primary dysmenorrhea (PDM) is not only a painful experience but also affects the psychological and affective states of women. Neuroimaging studies have revealed shared neural substrates for somatic and empathic pains in healthy subjects. However, little is known about the relationship between pain intensity and pain empathy in pain disorders. The cyclic nature of PDM makes it a unique model for investigating this issue during a patients' pain phase. To study how long-term pain modulates empathy for pain, T1-weighted magnetic resonance imaging scans were obtained in 39 PDM patients and 41 matched female healthy controls during menstruation. Subjects viewed static visual stimuli of the limbs submitted to painful and nonpainful stimulation to solicit empathy. The visual analogue scale for pain intensity and the Interpersonal Reactivity Index for empathic ability were also obtained. We found that women with PDM exhibited higher pain empathy compared with controls. The anterior insula and brain regions related to sensory discrimination with decreased gray matter volumes were not only shared but also acted as a mediator between pain intensity and pain empathy in PDM patients. In addition, the general linear modeling analysis revealed that long-term pain experience was a more important factor to pain empathy compared with pain intensity. This indicated that long-term pain may cause maladaptive brain structural plasticity, which may further affect psychological adjustment to bring patients more vivid pain when they witness suffering and distress in others., (Copyright © 2021 International Association for the Study of Pain.)

Primary dysmenorrhea (PDM), defined as painful menstrual cramps of uterine origin, could cause brain structural and functional changes after long-term menstrual pain. Here, we aimed to investigate the predictive value of uterine morphological features and microstructural/functional properties of the brain extracted from periovulatory phases for the intensity of menstrual pain as rated by women with PDM during their subsequent menstrual period. Forty-five women with PDM were recruited and classified into the high and mild pain intensity groups. Pelvic MRI was employed to extract the uterine texture features. White matter diffusion properties, grey matter and functional connectivity features were extracted as brain features. Multivariate logistic regression models with iteration optimization were built for classifying different pain intensity groups. Texture features from myometrium and uterine junction zone had outstanding prediction performance with an area under the receiver operating characteristic (AUC) of 0.96 (P < 0.05, permutation test), and diffusion properties along the thalamic fiber bundles were the most discriminative features with AUC of 0.95. Applying features from uterus and brain together, we could gain better prediction performance. Our results indicated that accumulated differences in menstrual pain were associated not only with uterine structure but also diffusion properties of thalamic-related fiber tracts, suggesting that treatment options of PDM patients may be expanded from only being able to manage pain in the uterus focusing on the functional/structural modifications of the pain processing system., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Primary dysmenorrhea (PDM) is cyclic menstrual pain in the absence of pelvic anomalies, and it is thought to be a sex-hormone related disorder. Existing study has focused on the effects of menstrual cramps on brain function and structure, ignoring the psychological changes associated with menstrual pain. Here we examined whether pain empathy in PDM differs from healthy controls (HC) using task-based functional magnetic resonance imaging (fMRI). Fifty-seven PDM women and 53 matched HC were recruited, and data were collected at the luteal and menstruation phases, respectively. During fMRI scans, participants viewed pictures displaying exposure to painful situations and pictures without any pain cues and assessed the level of pain experienced by the person in the picture. Regarding the main effect of the pain pictures, our results showed that compared to viewing neutral pictures, viewing pain pictures caused significantly higher activation in the anterior insula (AI), anterior cingulate cortex, and the left inferior parietal lobule; and only the right AI exhibited a significant interaction effect (group × picture). Post-hoc analyses confirmed that, relative to neutral pictures, the right AI failed to be activated in PDM women viewing painsss pictures. Additionally, there was no significant interaction effect between the luteal and menstruation phases. It suggests that intermittent pain can lead to abnormal empathy in PDM women, which does not vary with the pain or pain-free phase. Our study may deepen the understanding of the relationship between recurrent spontaneous pain and empathy in a clinical disorder characterized by cyclic episodes of pain., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Primary dysmenorrhoea (PDM), characterized as menstrual pain without pelvic pathology, is associated with pain-related negative mood and hormone fluctuations. Previous studies strongly supported the link between pain and negative mood in affected individuals; however, it remains largely unknown in patients with PDM., Methods: We focused on the effects how spontaneous pain, negative mood and hormone levels played on the central nervous system in 34 PDM women and 33 matched healthy controls across their cycles (periovulatory phase and menstruation phase) by using T1-weighted and functional imaging. Voxel-based morphometry and functional connectivity (FC) analyses were performed to evaluate brain structural and functional changes. Hormone concentrations (oestradiol, progesterone and cortisol) were also obtained., Results: Abnormal state-related GM volume in the amygdala was found between periovulatory and menstruation phases in PDM. Furthermore, larger amygdalar volume was observed in patients' menstruation phase, which was significantly correlated with higher levels of cortisol. In addition, we found increased amygdala-seeded FC in vlPFC, which may be associated with pain intensity and negative mood in PDM women during the pain state., Conclusions: Taken together, we found women with PDM had structural and functional abnormalities in the amygdala, which associated with stress hormone levels, pain intensity and negative mood, may reflect disturbed emotional and pain modulation in women with PDM., Significance: Our findings provide further evidence of amygdala-related abnormalities, which may be associated with pain-related affective distress and hormonal fluctuations in women with PDM, and complement the brain mechanism investigations for the pathophysiology of PDM., (© 2019 European Pain Federation - EFIC®.)

To develop a machine learning model to investigate the discriminative power of whole-brain gray-matter (GM) images derived from primary dysmenorrhea (PDM) women and healthy controls (HCs) during the pain-free phase and further evaluate the predictive ability of contributing features in predicting the variance in menstrual pain intensity. Sixty patients with PDM and 54 matched female HCs were recruited from the local university. All participants underwent the head and pelvic magnetic resonance imaging scans to calculate GM volume and myometrium-apparent diffusion coefficient (ADC) during their periovulatory phase. Questionnaire assessment was also conducted. A support vector machine algorithm was used to develop the classification model. The significance of model performance was determined by the permutation test. Multiple regression analysis was implemented to explore the relationship between discriminative features and intensity of menstrual pain. Demographics and myometrium ADC-based classifications failed to pass the permutation tests. Brain-based classification results demonstrated that 75.44% of subjects were correctly classified, with 83.33% identification of the patients with PDM (P < 0.001). In the regression analysis, demographical indicators and myometrium ADC accounted for a total of 29.37% of the variance in pain intensity. After regressing out these factors, GM features explained 60.33% of the remaining variance. Our results suggested that GM volume can be used to discriminate patients with PDM and HCs during the pain-free phase, and neuroimaging features can further predict the variance in the intensity of menstrual pain, which may provide a potential imaging marker for the assessment of menstrual pain intervention.

Neuroimaging studies have demonstrated the critical role of the insula in pain pathways and its close relation with the perceived intensity of nociceptive stimuli. We aimed to identify the structural and functional characteristics of the insula during periovulatory phase in women with primary dysmenorrhea (PDM), and further investigate its association with the intensity of perceived pain during menstruation. Optimized voxel-based morphometry and functional connectivity (FC) analyses were applied by using 3-dimensional T1-weighted and resting functional magnetic resonance imaging (fMRI) in 36 patients at the peri-ovulation phase and 29 age-, education-, and gender-matched healthy controls (HC). A visual analogue scale (VAS) was used to examine the intensity of the abdominal pain at periovulation and menstruation. In our results, PDM patients had significant higher VAS-rating during menstruaion than periovulation. Compared with the HC, PDM patients had lower gray matter density in the left anterior insula (aINS). Taken the left aINS as a seed region, we further found hypoconnectivity between aINS and medial prefrontal cortex (mPFC), which showed negative relation with the VAS during menstruation. As the aINS is a key site of the salience network (SN) and the mPFC is a critical region in the default mode network (DMN), it's implicated a trait-related central-alteration that communications between pain attention and perception networks were disrupted without the ongoing menstrual pain. Moreover, result of correlation analysis, at least in part, suggested a possible role of altered FC (pain-free period) in predicting pain perception (menstruation).

Primary dysmenorrhea (PD), as characterized by painful menstrual cramps without organic causes, is associated with central sensitization and brain function changes. Previous studies showed the integrated role of the default mode network (DMN) in the pain connectome and its key contribution on how an individual perceives and copes with pain disorders. Here, we aimed to investigate whether the cingulum bundle connecting hub regions of the DMN was disrupted in young women with PD. Diffusion tensor imaging was obtained in 41 PD patients and 41 matched healthy controls (HC) during their periovulatory phase. The production of prostaglandins (PGs) was obtained in PD patients during their pain-free and pain phases. As compared with HC, PD patients had similar scores of pain intensity, anxiety, and depression in their pain-free phase. However, altered white matter properties mainly located in the posterior section of the cingulum bundle were observed in PD. Besides PGs being related to menstrual pain, a close relationship was found between the white matter properties of the cingulum bundle during the pain-free phase and the severity of the menstrual pain in PD patients. Our study suggested that PD had trait changes of white matter integrities in the cingulum bundle that persisted beyond the time of menstruation. We inferred that altered anatomical connections may lead to less-flexible communication within the DMN, and/or between the DMN and other pain-related brain networks, which may result in the central susceptibility to develop chronic pain conditions in PD's later life. Hum Brain Mapp 38:4430-4443, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Empathy refers to the ability to understand someone else's emotions and fluctuates with the current state in healthy individuals. However, little is known about the neural network of empathy in clinical populations at different pain states. The current study aimed to examine the effects of long-term pain on empathy-related networks and whether empathy varied at different pain states by studying primary dysmenorrhea (PDM) patients. Multivariate partial least squares was employed in 46 PDM women and 46 healthy controls (HC) during periovulatory, luteal, and menstruation phases. We identified neural networks associated with different aspects of empathy in both groups. Part of the obtained empathy-related network in PDM exhibited a similar activity compared with HC, including the right anterior insula and other regions, whereas others have an opposite activity in PDM, including the inferior frontal gyrus and right inferior parietal lobule. These results indicated an abnormal regulation to empathy in PDM. Furthermore, there was no difference in empathy association patterns in PDM between the pain and pain-free states. This study suggested that long-term pain experience may lead to an abnormal function of the brain network for empathy processing that did not vary with the pain or pain-free state across the menstrual cycle. [ABSTRACT FROM AUTHOR]

The thalamus is a key region for the transmission of nociceptive information in the central modulation of pain and has been studied in the setting of numerous chronic pain conditions. Brain-derived neurotrophic factor (BDNF) is considered an important modulator for mediating nociceptive pathways in chronic pain. The present study aimed to investigate whether there was thalamus-related abnormal functional connectivity or relevant serum BDNF level alterations during periovulation in long-term primary dysmenorrhea (PDM). Thalamic subregions were defined according to the Human Brainnetome Atlas. Functional connectivity analyses were performed in 36 patients in the periovulatory phase and 29 age-, education-, and gender-matched healthy controls. Serum BDNF levels were evaluated by enzyme-linked immunosorbent assay and a significantly higher BDNF level was detected in PDM patients. Compared with HCs, PDM patients had abnormal functional connectivity of thalamic-subregions, mainly involving with prefrontal cortex, sensorimotor cortex, and temporal cortex. In addition, the functional connectivity of thalamic-subregions showed significant interactive effect correlated with serum BDNF level between PDM and HCs. It has been suggested that there were maladaptive or adoptive alteration associated with chronic menstrual pain even without the ongoing menstrual pain. BDNF might play a role in the development and chronicity of central nervous system dysfunction. These findings provided more accurate information about the involvement of the thalamus in the pathophysiology of PDM. [ABSTRACT FROM AUTHOR]

Abstract: Primary dysmenorrhea (PDM) is not only a painful experience but also affects the psychological and affective states of women. Neuroimaging studies have revealed shared neural substrates for somatic and empathic pains in healthy subjects. However, little is known about the relationship between pain intensity and pain empathy in pain disorders. The cyclic nature of PDM makes it a unique model for investigating this issue during a patients' pain phase. To study how long-term pain modulates empathy for pain, T1-weighted magnetic resonance imaging scans were obtained in 39 PDM patients and 41 matched female healthy controls during menstruation. Subjects viewed static visual stimuli of the limbs submitted to painful and nonpainful stimulation to solicit empathy. The visual analogue scale for pain intensity and the Interpersonal Reactivity Index for empathic ability were also obtained. We found that women with PDM exhibited higher pain empathy compared with controls. The anterior insula and brain regions related to sensory discrimination with decreased gray matter volumes were not only shared but also acted as a mediator between pain intensity and pain empathy in PDM patients. In addition, the general linear modeling analysis revealed that long-term pain experience was a more important factor to pain empathy compared with pain intensity. This indicated that long-term pain may cause maladaptive brain structural plasticity, which may further affect psychological adjustment to bring patients more vivid pain when they witness suffering and distress in others. [ABSTRACT FROM AUTHOR]