Brain morphological changes associated with cyclic menstrual pain

Abstract

Primary dysmenorrhea (PDM) is the most prevalent gynecological disorder for women in the reproductive age. PDM patients suffer from lower abdominal pain that starts with the onset of the menstrual flow. Prolonged nociceptive input to the central nervous system can induce functional and structural alterations throughout the nervous system. In PDM, a chronic viscero-nociceptive drive of cyclic nature, indications of central sensitization and altered brain metabolism suggest a substantial central reorganization. Previously, we hypothesized that disinhibition of orbitofrontal networks could be responsible for increased pain and negative affect in PDM. Here, we further tested this hypothesis. We used an optimized voxel-based morphometry (VBM) approach to compare total and regional gray matter (GM) increases and decreases in 32 PDM patients with 32 healthy age and menstrual cycle matched (peri-ovulatory phase) controls. Abnormal decreases were found in regions involved in pain transmission, higher level sensory processing, and affected regulation while increases were found in regions involved in pain modulation and in regulation of endocrine function. Moreover, GM changes in regions involved in top-down pain modulation and in generation of negative affect were related to the severity of the experienced PDM pain. Our results demonstrate that abnormal GM volume changes are present in PDM patients even in the absence of pain. These changes may underpin a combination of impaired pain inhibition, increased pain facilitation and increased affect. Our findings highlight that longer lasting central changes may occur not only in sustained chronic pain conditions but also in cyclic occurring pain conditions.

Effective Treatment of Chronic Low Back Pain in Humans Reverses Abnormal Brain Anatomy and Function

“…The left DLPFC was thinner and was activated abnormally in patients before treatment relative to controls; after treatment, the same region became thicker and also functioned more similarly to controls on a cognitive task. Previous research has shown altered brain anatomy in chronic pain conditions (Apkarian et al, 2004b;SchmidtWilcke et al, 2005SchmidtWilcke et al, , 2006Kuchinad et al, 2007;Buckalew et al, 2008;Geha et al, 2008;Lutz et al, 2008;Schweinhardt et al, 2008;Teutsch et al, 2008;Hsu et al, 2009;Obermann et al, 2009;Rodriguez-Raecke et al, 2009;Wood et al, 2009;Gwilym et al, 2010;Seminowicz et al, 2010;Tu et al, 2010), and other studies have linked cortical thickness to cognitive function (Hadjikhani et al, 2007;Dickerson et al, 2008;Sowell et al, 2008). To our knowledge, no other study has shown a link between gray matter density or cortical thickness loss and altered cognitive taskrelated brain activity in chronic pain.…”

Altered Brain Complexity in Women with Primary Dysmenorrhea: A Resting-State Magneto-Encephalography Study Using Multiscale Entropy Analysis

“…We speculate that the loss of complexity in PDMs could be attributed to the chronic stress elicited by recurrent menstrual pain. In our previous structural brain study, gray matter volume loss in regions of pain transmission, sensory processing, and affect regulation was found in PDMs [17]. Two resting-state fMRI studies reported trait-related hypoconnectivity between DMN and salience network during non-painful state [13,24].…”

“…Anterior cingulate cortex (ACC) engages in the emotional/motivational component of pain perception [125,126] and is a key region in the salience network (SAN) [102], which is activated when we constantly engage and focus on the pain but is normally deactivated when pain is gone. In a structural brain study [17], the gray matter volume of ACC was found the be increased in PDMs. We found that MSE in ACC is higher in PDMs compared to that in healthy controls, which suggest excessive attention processing of potential pain salience even in the absence of pain.…”

“…Two resting-state fMRI studies reported trait-related hypoconnectivity between DMN and salience network during non-painful state [13,24]. The loss of complexity in PDMs may result from inter-regional structural disconnections or decreased neuronal coupling interactions, and the possible underlying mechanisms include loss of neurons [17] or loss of local connectivity [13,24].…”

Steroid hormone hypersensitivity: clinical presentation and management

“…Recurrent miscarriage and peri-implantation embryo failure have been attributed to inappropriate immune responses, with an excess of proinflammatory T H 1 cytokines relative to T H 2/3 type cytokines. Low-grade inflammatory changes (12), oxidative stress (13), hypomagnesemia (14), and characteristic morphologic changes in the hypothalamus (15) have been associated with premenstrual mood changes, dysmenorrhea, and failure of assisted reproductive technologies.…”