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Migraine prevalence is three times higher in women than in men during fertile years, which is mainly due to sex hormone differences. The majority of women suffering from migraine without aura report improvement of their migraine attacks during pregnancy. Migraine attacks with aura can also improve during pregnancy, but more often remain the same or worsen. Anovulation caused by lactation is generally associated with a decrease in migraine attacks in breastfeeding women. This chapter describes the current knowledge on acute and prophylactic treatment options of migraine and other primary headache disorders during pregnancy and lactation. Further, clinical profiles of secondary headaches during pregnancy and the postpartum period are summarized.
Learn More >Toll-like receptor 4 (TLR4) recognizes exogenous pathogen-associated molecular patterns (PAMPs) and endogenous danger-associated molecular patterns (DAMPs) and initiates the innate immune response. Opioid receptors (μ, δ, and κ) activate inhibitory G-proteins and relieve pain. This review summarizes the following types of TLR4/opioid receptor pathway crosstalk: (a) Opioid receptor agonists non-stereoselectively activate the TLR4 signaling pathway in the central nervous system (CNS), in the absence of lipopolysaccharide (LPS). Opioids bind to TLR4, in a manner parallel to LPS, activating TLR4 signaling, which leads to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) expression and the production of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. (b) Opioid receptor agonists inhibit the LPS-induced TLR4 signaling pathway in peripheral immune cells. Opioids operate as pro-inflammatory cytokines, resulting in neuroinflammation in the CNS, but they mediate immunosuppressive effects in the peripheral immune system. It is apparent that TLR4/opioid receptor pathway crosstalk varies dependent on the cell type and activating stimulus. (c) Both the TLR4 and opioid receptor pathways activate the mitogen-activated protein kinase (MAPK) pathway. This crosstalk is located downstream of the TLR4 and opioid receptor signaling pathways. Furthermore, the classic opioid receptor can also produce pro-inflammatory effects in the CNS via MAPK signaling and induce neuroinflammation. (d) Opioid receptor agonists induce the production of high mobility group box 1 (HMGB1), an endogenous TLR4 agonist, supporting intercellular (neuron-to-glia or glia-to-neuron) interactions. This review also summarizes the potential effects of TLR4/opioid receptor pathway crosstalk on opioid analgesia, immune function, and gastrointestinal motility. Opioids non-stereoselectively activate the TLR4 pathway, and together with the subsequent release of pro-inflammatory cytokines such as IL-1 by glia, this TLR4 signaling initiates the central immune signaling response and modifies opioid pharmacodynamics. The DAMP HMGB1 is associated with the development of neuropathic pain. To explain morphine-induced persistent sensitization, a positive feedback loop has been proposed; this involves an initial morphine-induced amplified release of IL-1β and a subsequent exacerbated release of DAMPs, which increases the activation of TLR4 and the purinergic receptor P2X7R. Opioid receptor (μ, δ, and κ) agonists are involved in many aspects of immunosuppression. The intracellular TLR4/opioid receptor signaling pathway crosstalk induces the formation of the β-arrestin-2/TNF receptor-associated factor 6 (TRAF6) complex, which contributes to morphine-induced inhibition of LPS-induced TNF-α secretion in mast cells. A possible molecular mechanism is that the TLR4 pathway initially triggers the formation of the β-arrestin-2/TRAF6 complex, which is amplified by opioid receptor signaling, suggesting that β-arrestin-2 acts as a functional component of the TLR4 pathway.
Learn More >The review presents a systematic analysis of literature investigating the association between migraine and suicidal behaviors. Migraine is a common neurological disorder. The prevalence of migraines increases with age from adolescence to adulthood in both sexes, and results in a substantial loss of productivity due to missing days of school or work and need for bed rest. Literature prior to 2015 suggests that migraine is a predictor of suicide. Given the worldwide public health interest in suicide prevention, we examined the literature collected from diverse, predominantly non-European, populations post-2015. The databases used in this systematic review included: Medline, PsycINFO, EMBASE (Ovid), Science Direct (Elsevier), Cochrane, and PubMed for all available years of publication from January 2015 onwards. The review included participants aged 16 and over who had been diagnosed with migraines with the following outcome variables: any suicidality, both fatal and non-fatal; suicidal ideation; and suicidal behavior. The database searches yielded a total of 542 citations. Following title and abstract screening, 460 articles were excluded and a total of 21 citations were evaluated. After full-text review and excluding a further 11 non-eligible studies, a total of 10 studies were eligible for inclusion in the systematic review. Current existing research highlights the important association between the increased risk of suicidal behaviors in the clinical and general population among chronic migraineurs with/without aura worldwide. Future studies are needed to facilitate the development of clinical guidelines for risk assessment, targeted interventions, and evidence-based treatment of migraine to reduce the risk of suicide among this vulnerable population.
Learn More >Endometriosis is a systemic and chronic condition in women of childbearing age, yet a highly enigmatic disease with unresolved questions: there are no known biomarkers, nor established clinical stages. We here investigate the use of patient-generated health data and data-driven phenotyping to characterize endometriosis patient subtypes, based on their reported signs and symptoms. We aim at unsupervised learning of endometriosis phenotypes using self-tracking data from personal smartphones. We leverage data from an observational research study of over 4000 women with endometriosis that track their condition over more than 2 years. We extend a classical mixed-membership model to accommodate the idiosyncrasies of the data at hand, i.e., the multimodality and uncertainty of the self-tracked variables. The proposed method, by jointly modeling a wide range of observations (i.e., participant symptoms, quality of life, treatments), identifies clinically relevant endometriosis subtypes. Experiments show that our method is robust to different hyperparameter choices and the biases of self-tracking data (e.g., the wide variations in tracking frequency among participants). With this work, we show the promise of unsupervised learning of endometriosis subtypes from self-tracked data, as learned phenotypes align well with what is already known about the disease, but also suggest new clinically actionable findings. More generally, we argue that a continued research effort on unsupervised phenotyping methods with patient-generated health data via new mobile and digital technologies will have significant impact on the study of enigmatic diseases in particular, and health in general.
Learn More >Chronic pain is often multifactorial and accompanied by psychological distress, catastrophizing thoughts, reduced physical function, and socio-economic worries. In this explorative study, we investigated potential mediators in the relationships of psychological and demographic variables with chronic pain and physical function in women and men.
Learn More >Chronic pain and fatigue are two cardinal features of ankylosing spondylitis (AS) and how to effectively treat these conditions continues to be a challenge. The underlying mechanisms and the relationship between AS-related pain and fatigue remain poorly understood. The present study was conducted, therefore, to explore the brain functional and structural changes associated with pain and fatigue in AS. A total of 65 AS patients (48 men and 17 women; 32.33 ± 8.6 years) and 53 age- and sex-matched controls were enrolled in the study. The patients underwent clinical assessment based on Total Back Pain scores, Fatigue Severity Scale, Bath Ankylosing Spondylitis Disease Activity Index, (BASDAI), high-sensitivity C-reactive Protein (hsCRP), erythrocyte sedimentation rate (ESR), and Beck Depression Inventory (BDI). Using 3T magnetic resonance imaging (3T-MRI), we analyzed the brain functional (connectivity and nodal properties) and structural (covariance and gray matter volumes) differences between AS patients and controls. Furthermore, we extracted the values of the significantly changed regions in the AS cohort and explored their association with pain and fatigue. In AS patients, there were functional and structural abnormalities distributed in the default mode network (DMN), salience network (SN), sensory/somatomotor network (SMN), dorsal attention network (DAN), task control network (TCN), and visual network, and some regions showed both types of changes. Among these, the functional connectivity (FC) between the left insula and medial prefrontal cortex, the betweenness centrality of the left medial prefrontal cortex and the gray matter volume of the right putamen tracked both pain and fatigue. In addition, pain was related to within-DMN FC disruption and nodal function / gray matter volumes changes in DMN, SN, and the visual network, while fatigue mainly involved the SMN, DAN, and TCN. Moreover, certain changes were also related to BASDAI and inflammation level. This study offers new insights into understanding the neural mechanism of AS-related pain and fatigue, and could help to stratify patients based on the correlation features and ultimately move towards a personalized therapy.
Learn More >Chronic pain is common in adolescents. Evidence-based guidelines recommend interdisciplinary treatment, but access is limited by geography. The development of hybrid programs utilizing both face-to-face and videoconference treatment may help overcome this. We developed a 7-week hybrid pediatric interdisciplinary pain program (Hybrid-PIPP) and wished to compare it to individual face-to-face sessions (Standard Care). Our objective was to test the feasibility of a protocol that used a matched pair un-blinded randomized controlled design to investigate the efficacy and cost-effectiveness of the Hybrid-PIPP compared to Standard Care.
Learn More >Measuring health-related quality of life (HRQOL) in patients with chronic low back pain (LBP) is crucial to monitor and improve the patients' health status through effective rehabilitation. While the 12-item short-form health survey (SF-12) was developed as a shorter alternative to the 36-item short-form health survey for assessing HRQOL in large-scale studies, to date, no cross-culturally adapted and validated Hausa version exists. This study aimed to translate and cross-culturally adapt the SF-12 into Hausa language, and test its psychometric properties in mixed urban and rural Nigerian populations with chronic LBP.
Learn More >Pain and body perception are essentially two subjective mutually influencing experiences. However, in the field of musculoskeletal disorders and rheumatic diseases we lack of a comprehensive knowledge about the relationship between body perception dysfunctions and pain or disability. We systematically mapped the literature published about the topics of: (a) somatoperception; (b) body ownership; and (c) perception of space, analysing the relationship with pain and disability. The results were organized around the two main topics of the assessment and treatment of perceptual dysfunctions. This scoping review followed the six-stage methodology suggested by Arksey and O'Malley. Ten electronic databases and grey literature were systematically searched. The PRISMA Extension for Scoping Reviews was used for reporting results. Two reviewers with different background, independently performed study screening and selection, and one author performed data extraction, that was checked by a second reviewer. Thirty-seven studies fulfilled the eligibility criteria. The majority of studies (68%) concerned the assessment methodology, and the remaining 32% investigated the effects of therapeutic interventions. Research designs, methodologies adopted, and settings varied considerably across studies. Evidence of distorted body experience were found mainly for explicit somatoperception, especially in studies adopting self-administered questionnaire and subjective measures, highlighting in some cases the presence of sub-groups with different perceptual features. Almost half of the intervention studies (42%) provided therapeutic approaches combining more than one perceptual task, or sensory-motor tasks together with perceptual strategies, thus it was difficult to estimate the relative effectiveness of each single therapeutic component. To our knowledge, this is the first attempt to systematically map and summarize this research area in the field of musculoskeletal disorders and rheumatic diseases. Although methodological limitations limit the validity of the evidence obtained, some strategies of assessment tested and therapeutic strategies proposed represent useful starting points for future research. This review highlights preliminary evidence, strengths, and limitations of the literature published about the research questions, identifying key points that remain opened to be addressed, and make suggestions for future research studies. Body representation, as well as pain perception and treatment, can be better understood if an enlarged perspective including body and space perception is considered.
Learn More >Vestibular migraine (VM) is the most common cause of spontaneous vertigo with no specific physical and laboratory examinations, and is an under-recognized entity with substantial burden for the individual and the society. In this study, by observing the brainstem auditory evoked potential (BAEP) and cognitive function of VM patients, the possible laboratory diagnostic indicators of VM and the influence of disease on cognitive function were discussed. The study included 78 VM patients, 76 migraine patients, and 79 healthy individuals. The age, gender, and other clinical history of the three groups matched. All participants underwent BAEP examinations, in which patients in the migraine group and outpatients of the VM group were in the interictal period, and inpatients in the VM group were examined during episodes, while all patients tested for the Addenbrooke's cognitive examination-revised (ACE-R) scale were in the interictal period. The differences in BAEP and ACE-R scores between the three groups of members and their relationship with the clinical features of VM patients were analyzed. The peak latency of I, III, and V wave in the BAEP of the VM group was longer than that of the migraine group and the control group ( < 0.05). The peak latency of V wave in the BAEP of the migraine group was longer than that of the control group ( < 0.05). The ACE-R of the VM group scored lower than the migraine group in terms of language fluency and language ( < 0.05), and lower than the control group in terms of total score, language fluency, language, and visuospatial ( < 0.05); and the ACE-R of the migraine group scored lower than the control group in the total score and visuospatial ( < 0.05). Migraine patients have brainstem dysfunction, and VM patients have more severe brainstem dysfunction than migraine patients, suggesting that VM patients have both central nervous system damage and peripheral nerve damage. Migraine patients have cognitive impairment, while cognitive impairment in VM patients is more severe than in migraine patients.
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