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Atopic dermatitis (AD) is among the most frequent inflammatory skin diseases in humans, affecting up to 20% of children and 10% of adults in higher income countries. Chronic pruritus is a disease-defining symptom of AD, representing the most burdensome symptom for patients. Severe chronic pruritus causes significant sleep disturbances and impaired quality of life, as well as increased anxiety, depression and suicidal behavior. Until recently, skin care, topical corticosteroids, and calcineurin-inhibitors were primarily used to treat mild to moderate AD, while phototherapy and immunosuppressive agents such as corticosteroids, cyclosporine, and methotrexate were used to treat patients with moderate to severe AD. The potential short- and long-term adverse events associated with these treatments or their insufficient therapeutic efficacy limited their use in controlling pruritus and eczema in AD patients over longer periods of time. As our understanding of AD pathophysiology has improved and new systemic and topical treatments have appeared on the market, targeting specific cytokines, receptors, or their intracellular signaling, a new era in atopic dermatitis and pruritus therapy has begun. This review highlights new developments in AD treatment, placing a specific focus on their anti-pruritic effects.
Learn More >The growing awareness of the critical role played by the innate and adaptive immune systems in the mechanisms underlying chronic pain has prompted further research examining the modalities by which immune cells communicate with neurones, the aim being to identify new players involved in inflammatory and neuropathic pain signalling. This collection of research includes 9 articles on neuroimmune interactions as the underlying mechanisms for neuropathic pain including peripheral neuropathies, pain in rheumatoid arthritis and osteoarthritis, and bone cancer pain. The immune cells under scrutiny include macrophages, microglia, osteoclasts, and B cells, and their interactions with neurones in locations such as the dorsal root ganglia, blood-spinal cord barrier, spinal cord, and brain. Our hope is that this body of work may serve to furnish existing interest while also constituting a springboard of sorts for indispensable further investigation on neuroimmune interactions in chronic pain.
Learn More >There is very limited data on women with migraine disease as they age and transition to menopause. Despite evidence for the increased burden of the disease during this transition, there is no data on the association between migraine and allostatic load as a marker of cumulative biological risk. We aimed to determine whether women with migraine suffer from higher levels of allostatic load during perimenopausal transition. A total of 2,105 perimenopausal women from the first wave of the Study of Women's Health Across the Nation (SWAN) were included in this study. Allostatic Load (AL) score was estimated for each participant from the measurements of: systolic and diastolic blood pressure, C-reactive protein level, high-density lipoprotein cholesterol level, total cholesterol level, waist-to-hip ratio, fasting serum glucose, triglycerides, and dehydroepiandrosterone levels. Of the 2,105 participants included in the study, there were 369 migraineurs and 1,730 controls. Migraineurs had 63% higher odds of increased load score (odds ratio 1.63; 95% confidence interval, 1.17-2.29). Compared to controls, migraineurs were more likely to experience sleep problems in the univariate analysis, however despite the high burden of sleep problems, there were no significant associations between allostatic load and sleep disturbances in perimenopausal women with migraine after controlling for other factors. This is the first study to systematically and quantitatively examine allostatic load in migraine patients. The findings establish that migraineurs are more likely to experience higher allostatic load than their non-migraine counterparts during perimenopausal transition. The findings encourage new lines of investigation for lowering the burden of the disease through interventions that modify the levels of allostatic load biomarkers examined in this study.
Learn More >Migraine is a common neurological disorder which affects 15-20% of the population; it has a high socioeconomic impact through treatment and loss of productivity. Current forms of diagnosis are primarily clinical and can be difficult owing to comorbidity and symptom overlap with other neurological disorders. As such, there is a need for better diagnostic tools in the form of genetic testing. Migraine is a complex disorder, encompassing various subtypes, and has a large genetic component. Genetic studies conducted on rare monogenic subtypes, including familial hemiplegic migraine, have led to insights into its pathogenesis via identification of causal mutations in three genes (, and ) that are involved in transport of ions at synapses and glutamatergic transmission. Study of familial migraine with aura pedigrees has also revealed other causal genes for monogenic forms of migraine. With respect to the more common polygenic form of migraine, large genome-wide association studies have increased our understanding of the genes, pathways and mechanisms involved in susceptibility, which are largely involved in neuronal and vascular functions. Given the preponderance of female migraineurs (3:1), there is evidence to suggest that hormonal or X-linked components can also contribute to migraine, and the role of genetic variants in mitochondrial DNA in migraine has been another avenue of exploration. Epigenetic studies of migraine have shown links between hormonal variation and alterations in DNA methylation and gene expression. While there is an abundance of preliminary studies identifying many potentially causative migraine genes and pathways, more comprehensive genomic and functional analysis to better understand mechanisms may aid in better diagnostic and treatment outcomes.
Learn More >Chronic neuropathic pain (CNP) is caused by a lesion or disease of the somatosensory nervous system. It affects ~8% of the general population and negatively impacts a person's level of functioning and quality of life. Its resistance to available pain therapies makes CNP a major unmet medical need. Immune cells have been shown to play a role for development, maintenance and recovery of CNP and therefore are attractive targets for novel pain therapies. In particular, in neuropathic mice and humans, microglia are activated in the dorsal horn and peripheral immune cells infiltrate the nervous system to promote chronic neuroinflammation and contribute to the initiation and progression of CNP. Importantly, immunity not only controls pain development and maintenance, but is also essential for pain resolution. In particular, regulatory T cells, a subpopulation of T lymphocytes with immune regulatory function, and macrophages were shown to be important contributors to pain recovery. In this review we summarize the interactions of the peripheral immune system with the nervous system and outline their contribution to the development and recovery of pain.
Learn More >Fibromyalgia (FM) and complex regional pain syndrome (CRPS) share many pathological mechanisms related to chronic pain and neuroinflammation, which may contribute to the multifactorial pathological mechanisms in both FM and CRPS. The aim of this study was to assess neuroinflammation in FM patients compared with that in patients with CRPS and healthy controls.
Learn More >Fibromyalgia and myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) are poorly understood conditions with overlapping symptoms, fuelling debate as to whether they are manifestations of the same spectrum or separate entities. Both are associated with hypermobility, but this remains significantly undiagnosed, despite impact on quality of life.
Learn More >In some patients, migraine attacks are associated with symptoms of allodynia which can be localized (cephalic) or generalized (extracephalic). Using functional neuroimaging and cutaneous thermal stimulation, we aimed to investigate the differences in brain activation of patients with episodic migraine (n = 19) based on their allodynic status defined by changes between ictal and interictal pain tolerance threshold for each subject at the time of imaging. In this prospective imaging study, differences were found in brain activity between the ictal and interictal visits in the brainstem/pons, thalamus, insula, cerebellum and cingulate cortex. Significant differences were also observed in the pattern of activation along the trigeminal pathway to noxious heat stimuli in no allodynia vs. generalized allodynia in the thalamus and the trigeminal nucleus but there were no activation differences in the trigeminal ganglion. The functional magnetic resonance imaging (fMRI) findings provide direct evidence for the view that in migraine patients who are allodynic during the ictal phase of their attacks, the spinal trigeminal nucleus and posterior thalamus become hyper-responsive (sensitized)-to the extent that they mediate cephalic and extracephalic allodynia, respectively. In addition, descending analgesic systems seem as "switched off" in generalized allodynia.
Learn More >Although the widely used single L-enantiomers of local anesthetics have less toxic effects on the cardiovascular and central nervous systems, the mechanisms mediating their antinociceptive actions are not well understood. The authors hypothesized that significant differences in the ion channel blocking abilities of the enantiomers of bupivacaine would be identified.
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