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Migraine and stroke are among the most prevalent and disabling neurological diseases. Epidemiologic studies showed that there is an association between migraine and stroke. Migraineurs, especially those with aura, are more likely to develop subclinical infarct-like lesions in the brain and are at risk for cryptogenic or cardioembolic stroke. Migrainous headache can be found at the onset of acute ischemic stroke in some patients, and in rare instances, an infarction can be directly attributed to a prolonged migraine aura, ie, migrainous infarction. Importantly, recent studies suggest that in the event of cerebral artery occlusion, even a history of migraine is sufficient to accelerate infarct progression and worsen outcomes. The mechanisms underlying the migraine-stroke connection are multifactorial, with genetic predisposition, aura-related electrophysiological mechanisms (cortical spreading depolarization), and cerebral microembolism being the most convincing ones at this point. Here, we provide a comprehensive overview on recent imaging studies that have helped us better understand the complex association between migraine and stroke.
Learn More >Previous studies found higher levels of pain severity and disability to be associated with higher costs and lower health-related quality of life. However, these findings were based on cross-sectional data and little is known about the longitudinal relationships between pain severity and disability versus health-related quality of life and costs among chronic low back pain patients. This study aims to cover this knowledge gap by exploring these longitudinal relationships in a consecutive cohort.
Learn More >Understanding the functional dynamics of neural oscillations in the sensory thalamus is essential for elucidating the perception and modulation of neuropathic pain. Local field potentials were recorded from the sensory thalamus of twelve neuropathic pain patients. Single and combinational neural states were defined by the activity state of a single or paired oscillations. Relationships between the duration or occurrence rate of neural state and pre-operative pain level or pain relief induced by deep brain stimulation were evaluated. Results showed that the occurrence rate of the single neural state of low-beta oscillation was significantly correlated with pain relief. The duration and occurrence rate of combinational neural states of the paired low-beta with delta, theta, alpha, high-beta or low-gamma oscillations were more significantly correlated with pain relief than the single neural states. Moreover, these significant combinational neural states formed a local oscillatory network with low-beta oscillation as a key node. The results also showed correlations between measures of combinational neural states and subjective pain level as well. The duration of combinational neural states of paired alpha with delta or theta oscillations and the occurrence rate of neural states of the paired delta with low-beta or low-gamma oscillations were significantly correlated with pre-operative pain level. In conclusion, this study revealed that the integration of oscillations and the functional dynamics of neural states were differentially involved in modulation and perception of neuropathic pain. The functional dynamics could be biomarkers for developing neural state dependent deep brain stimulation for neuropathic pain. This article is protected by copyright. All rights reserved.
Learn More >Nemolizumab targets the interleukin 31 receptor alpha subunit (IL-31RA) involved in atopic dermatitis (AD) pathogenesis.
Learn More >The role of the trigeminal autonomic reflex in headache syndromes, such as cluster headache, is undisputed but sparsely investigated. The aim of the present study was therefore, to identify neural correlates that play a role in the initiation of the trigeminal autonomic reflex. We further aimed to discriminate between components of the reflex that are involved in nociceptive compared to non-nociceptive processing.
Learn More >Chronic pain is highly prevalent among patients with mood, anxiety, personality, and somatic symptom disorders; and patients with chronic pain often suffer from persistent interpersonal distress. However, the neural mechanisms underlying this phenomenon and its possible role in the etiology of chronic pain are not yet understood. Based on our Developmental Theory of Centralized/Somatoform Pain, and prior research suggesting the existence of a shared neural system subserving interpersonal emotions and pain, we aimed to identify the neural basis for modulation of pain by feelings of interpersonal rejection and the role of the early interpersonal environment in development of this shared neural system.
Learn More >Chemotherapy-induced neuropathic pain is a dose-limiting side effect of many cancer therapies due to their propensity to accumulate in peripheral nerves, which is facilitated by the permeability of the blood-nerve barrier. Preclinically, the chemotherapy agent vincristine (VCR) activates endothelial cells in the murine peripheral nervous system and in doing so allows the infiltration of monocytes into nerve tissue where they orchestrate the development of VCR-induced nociceptive hypersensitivity. In this study we demonstrate that VCR also activates endothelial cells in the murine central nervous system, increases paracellular permeability and decreases trans endothelial resistance. In in vivo imaging studies in mice, VCR administration results in trafficking of inflammatory monocytes through the endothelium. Indeed, VCR treatment affects the integrity of the blood-spinal cord-barrier as indicated by Evans Blue extravasation, disrupts tight junction coupling and is accompanied by the presence of monocytes in the spinal cord. Such inflammatory monocytes (Iba-1 CCR2 Ly6C TMEM119 cells) that infiltrate the spinal cord also express the pro-nociceptive cysteine protease Cathepsin S. Systemic treatment with a CNS-penetrant, but not a peripherally-restricted, inhibitor of Cathepsin S prevents the development of VCR-induced hypersensitivity, suggesting that infiltrating monocytes play a functional role in sensitising spinal cord nociceptive neurons. Our findings guide us towards a better understanding of central mechanisms of pain associated with VCR treatment and thus pave the way for the development of innovative antinociceptive strategies.
Learn More >Opioid drugs are the gold standard for the management of pain, but their use is severely limited by dangerous and unpleasant side effects. All clinically available opioid analgesics bind to and activate the mu-opioid receptor (MOR), a heterotrimeric G-protein-coupled receptor, to produce analgesia. The activity of these receptors is modulated by a family of intracellular RGS proteins or regulators of G-protein signaling proteins, characterized by the presence of a conserved RGS Homology (RH) domain. These proteins act as negative regulators of G-protein signaling by serving as GTPase accelerating proteins or GAPS to switch off signaling by both the Gα and βγ subunits of heterotrimeric G-proteins. Consequently, knockdown or knockout of RGS protein activity enhances signaling downstream of MOR. In this review we discuss current knowledge of how this activity, across the different families of RGS proteins, modulates MOR activity, as well as activity of other members of the opioid receptor family, and so pain and analgesia in animal models, with particular emphasis on RGS4 and RGS9 families. We discuss inhibition of RGS proteins with small molecule inhibitors that bind to sensitive cysteine moieties in the RH domain and the potential for targeting this family of intracellular proteins as adjuncts to provide an opioid sparing effect or as standalone analgesics by promoting the activity of endogenous opioid peptides. Overall, we conclude that RGS proteins may be a novel drug target to provide analgesia with reduced opioid-like side effects, but that much basic work is needed to define the roles for specific RGS proteins, particularly in chronic pain, as well as a need to develop newer inhibitors.
Learn More >Enhanced postoperative recovery programmes (ERAS) were developed about 20 years ago based on improved understanding of the pathophysiology of postoperative recovery within an integrated multidisciplinary approach. The results across surgical procedures have been extremely positive with a reduction in hospitalisation and medical complications, without increased re-admission rates. However, several challenges lie ahead including improved implementation of existing scientific evidence, increased focus on post-discharge recovery problems and a need for improved design of future ERAS studies. However, the most important challenges lie within a better understanding and control of undesirable peri-operative pathophysiological responses with subsequent risk of organ dysfunction. These efforts should focus on: the inflammatory and neurohumoral surgical stress responses; fluid management; pain management; blood management; mechanisms of orthostatic intolerance; postoperative cognitive dysfunction; risk factors for thrombo-embolic complications; and mechanisms and prevention of postoperative ileus. Finally, more focus should be made on the different barriers to post-discharge functional recovery and the choice of (pre- and postoperative) rehabilitation. These efforts should be made on a procedure-specific as well as on a patient-specific basis.
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