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Migraineurs are hypersensitive for most sensory domains like visual, auditory or somatosensory processing even outside of attacks. This behavioral peculiarity is mirrored by findings of cortical hyper-responsivity already in the interictal state. Using repetitive visual stimulation to elicit steady state visually evoked potentials (SSVEP) in 30 interictal episodic migraineurs and 30 controls we show hyper-responsivity of the visual cortex in the migraineurs. Additionally, the occipital regions were remarkably stronger coupled to the temporal, premotor and the anterior cingulate cortex than in headache free controls. These data suggest harmonized oscillations of different cortical areas as a response to visual input which might be driven by the cuneus. Furthermore, the increased coupling is modulated by the current state of the migraine cycle as the coupling was significantly stronger in patients with longer interictal periods.
Learn More >Migraines with aura have been associated with suicide in adolescents and young adults, but the association between suicide and migraine frequency has not been determined. This study investigated suicidal ideation and suicide attempts among patients with varying frequencies of migraines, with and without auras. This cross-sectional study analyzed 528 patients aged between 20 and 60 years from a headache outpatient clinic in Taiwan. All patients completed a set of questionnaires, including a demographic questionnaire, the Migraine Disability Assessment questionnaire, the Hospital Anxiety and Depression Scale, the Beck Depression Inventory, and the Pittsburgh Sleep Quality Index. Suicide risk was evaluated by self-reported lifetime suicidal ideation and attempts. Patients were divided into low-frequency (1-4 days/month), moderate-frequency (5-8 days/month), high-frequency (9-14 days/month), and chronic (≥15 days/month) migraine groups. The association between migraine frequency and suicidality was investigated using multivariable linear regression and logistic regression. The rates of suicidal ideation and suicide attempts were the highest for chronic migraine with aura (ideation: 47.2%; attempts: 13.9%) and lowest in migraine-free controls (2.8%). Migraine frequency was an independent risk factor for suicidal ideation and attempts in patients with aura (both < 0.001), but not in patients without auras. Migraine aura and depression were associated with higher risks of suicidal ideation and suicide attempts in patients with migraine. High migraine frequency has a correlation with high suicide risk in patients who experience an aura, but not in other patients with migraine.
Learn More >Opioid prescriptions for chronic pain and subsequent opioid-related complications have risen dramatically in the US. Recent data suggest that medical marijuana laws have been associated with lower state-level opioid overdose mortality. In a national survey, we examined the prevalence of substitution of marijuana for opioids among US adults taking opioids for pain.Using GfK's KnowledgePanel, we conducted an Internet-based survey of a nationally representative sample of 16,280 adults in 2017 about individual perceptions and use of marijuana. We developed questions designed to assess the extent and reasons for substitution of marijuana for opioids. We examined opioid substitution among respondents with a history of ever using marijuana who used opioids in the past 12 months. There were 9,003 respondents, corresponding to a 55.3% response rate. The mean age was 48 years. Among the 5% (n = 486) who reported ever using marijuana and using opioids in the past year, 43% used opioids daily, and 23% reported current (past 30 day) marijuana use. Forty-one percent reported a decrease or cessation of opioid use due to marijuana use; 46% reported no change in opioid use; and 8% reported an increase in opioid use. We found that a substantial number of US adults reported that they substituted marijuana for opioids.
Learn More >Therapeutic virtual reality (VR) has emerged as an effective, drug-free tool for pain management, but there is a lack of randomized, controlled data evaluating its effectiveness in hospitalized patients. We sought to measure the impact of on-demand VR versus "health and wellness" television programming for pain in hospitalized patients.
Learn More >Research has indicated that calcitonin gene-related peptide (CGRP) receptor antagonists can be effective in the acute treatment of migraine. Six major drugs are included within this category: telcagepant, olcegepant, BI 44370, rimegepant (BMS-927711), MK3207, and ubrogepant. However, no previous studies have performed network meta-analyses to directly compare the effects of these drugs. In the present study, we assessed the therapeutic qualities of these six different drugs to inform further clinical research. We searched PubMed, Embase, Ovid MEDLINE, Web of Science, and the Cochrane Central Register for Controlled Trials for relevant randomized controlled trials (RCTs) published through to October 2018. Two reviewers performed a network meta-analysis of efficacy and toxicity on the basis of odds ratios (ORs). Ten randomized controlled trials involving 8,174 patients were included in our analysis. Olcegepant (OR: 4.09; CI: 1.81, 9.25), ubrogepant (OR: 2.11; CI: 1.10, 4.05), and BI 44370 (OR: 3.36; CI: 2.24, 5.04) were more effective in ensuring pain relief 2 h after treatment than was placebo treatment. BI 44370 was associated with an increased risk of adverse events when compared with placebo treatment (OR: 1.57; CI: 1.32, 1.88). Surface under the cumulative ranking curve analysis revealed that olcegepant was most effective and ubrogepant was associated with the lowest risk of adverse events among the six treatment options. Olcegepant was more effective, and ubrogepant had lower toxicity than the remaining treatments. CGRP antagonists are promising for the acute treatment of migraine, especially among patients who are unable to take triptans.
Learn More >: Chronic pain is a common comorbid complaint in traumatized refugees seeking treatment for posttraumatic stress disorder (PTSD) and depression. However, the effect of comorbid pain on treatment remains under investigated. : To investigate whether pre-treatment pain (severity/interference) predicts outcomes in a multimodal treatment targeting PTSD, depression, anxiety, somatic complaints, and health-related disability in refugees exposed to torture and organized violence. Additional predictors were gender, age, and number of treatment sessions. : Participants were active cases at a specialist outpatient clinic for tortured refugees (n = 276; 170 men, 106 women) who were either on a treatment waitlist (mean length = 7.4 months, SD = 4.5), in treatment (mean length = 12.2 months, SD = 6.5), or who completed treatment and had (or were waiting for) a follow-up assessment. Participants completed symptom measures at referral, pre- and post-treatment, and 9-month follow-up. Multi-level mixed modelling was used to assess whether outcomes at post-treatment and 9-months were predicted by pain, gender, age, or the number of treatment sessions. : Treatment yielded significant pre-to-post-treatment reductions in PTSD, depression, anxiety, and number of pain locations, but no reductions in pain severity/interference, or health-related disability, except for societal participation. Gains for PTSD, depression, and societal participation were maintained at the 9-month follow-up. Higher levels of pain interference (but not severity) predicted poorer outcomes (PTSD, depression, and anxiety). Age, gender and number of treatment sessions did not predict outcomes, except for a small negative effect of (older) age on PTSD. : A growing body of literature suggests that pain and PTSD symptoms interact in ways to increase the severity and impact of both disorders in refugee and non-refugee populations alike. The present study suggests interference from pain can lessen the effectiveness of standard multi-modal treatments for refugees.
Learn More >Although the clinical features and pathophysiology of complex regional pain syndrome (CRPS) have been studied in the peripheral and central nervous systems, few plausible pathological interactions are known among the metabolites in these systems. Thus, the purpose of this study was to investigate abnormal relationships and interactions between peripheral metabolites and central neurometabolites in patients with CRPS.
Learn More >Chronic pain patients frequently suffer from psychological symptoms. There is no consensus concerning the prevalence of severe anxiety and depressive symptoms and the strength of the associations between pain intensity and psychological distress. Although an important aspect of the clinical picture is understanding how the pain condition impacts life, little is known about the relative importance of pain and psychological symptoms for individual's life impact. The aims of this study were to identify subgroups of pain patients; to analyze if pain, psychological distress, and life impact variables influence subgrouping; and to investigate how patients in the subgroups benefit from treatments.
Learn More >African Americans disproportionately suffer more severe and debilitating morbidity from chronic pain than do non-Hispanic Whites. These differences may arise from differential exposure to psychosocial and environmental factors such as adverse childhood experiences, racial discrimination, low socioeconomic status, and depression, all of which have been associated with chronic stress and chronic pain. Race, as a social construct, makes it such that African Americans are more likely to experience different early life conditions, which may induce epigenetic changes that sustain racial differences in chronic pain. Epigenetics is one mechanism by which environmental factors such as childhood stress, racial discrimination, economic hardship, and depression can affect gene expression without altering the underlying genetic sequence. This article provides a narrative review of the literature on epigenetics as a mechanism by which differential environmental exposure could explain racial differences in chronic pain. Most studies of epigenetic changes in chronic pain examine DNA methylation. DNA methylation is altered in the glucocorticoid (stress response) receptor gene, , which has been associated with depression, childhood stress, low socioeconomic status, and chronic pain. Similarly, DNA methylation patterns of immune cytokine genes have been associated with chronic stress states. Thus, DNA methylation changes may play an essential role in the epigenetic modulation of chronic pain in different races with a higher incidence of epigenetic alterations contributing to more severe and disabling chronic pain in African Americans.
Learn More >Type A γ-aminobutyric acid (GABA) receptors are pentameric ligand-gated ion channels and the main drivers of fast inhibitory neurotransmission in the vertebrate nervous system. Their dysfunction is implicated in a range of neurological disorders, including depression, epilepsy and schizophrenia. Among the numerous assemblies that are theoretically possible, the most prevalent in the brain are the α1β2/3γ2 GABA receptors. The β3 subunit has an important role in maintaining inhibitory tone, and the expression of this subunit alone is sufficient to rescue inhibitory synaptic transmission in β1-β3 triple knockout neurons. So far, efforts to generate accurate structural models for heteromeric GABA receptors have been hampered by the use of engineered receptors and the presence of detergents. Notably, some recent cryo-electron microscopy reconstructions have reported 'collapsed' conformations; however, these disagree with the structure of the prototypical pentameric ligand-gated ion channel the Torpedo nicotinic acetylcholine receptor, the large body of structural work on homologous homopentameric receptor variants and the logic of an ion-channel architecture. Here we present a high-resolution cryo-electron microscopy structure of the full-length human α1β3γ2L-a major synaptic GABA receptor isoform-that is functionally reconstituted in lipid nanodiscs. The receptor is bound to a positive allosteric modulator 'megabody' and is in a desensitized conformation. Each GABA receptor pentamer contains two phosphatidylinositol-4,5-bisphosphate molecules, the head groups of which occupy positively charged pockets in the intracellular juxtamembrane regions of α1 subunits. Beyond this level, the intracellular M3-M4 loops are largely disordered, possibly because interacting post-synaptic proteins are not present. This structure illustrates the molecular principles of heteromeric GABA receptor organization and provides a reference framework for future mechanistic investigations of GABAergic signalling and pharmacology.
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