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Schwannomatosis and neurofibromatosis type 2 (NF2) are two distinct neuro-genetic tumor predisposition disorders which however share some clinical and genetic features. While germline mutations in the NF2 gene are only found in NF2, a majority of schwannomatosis patients have germline mutations in the SMARCB1 or LZTR1 genes. The overlapping clinical phenotypes pose a serious challenge in differential diagnosis and in risk stratification of these two entities which is further complicated by frequent mosaicism in both disorders. Chronic neuropathic pain which is a typical consequence of small fiber neuropathy, is characteristic for schwannomatosis. By contrast, NF2 patients do not have chronic pain but may have moderate to severe sensory deficits and paresis which are not characteristic for schwannomatosis. In the present study, we determined intra-epidermal nerve fiber density (IEND) in skin biopsies of 34 clinically ascertained schwannomatosis and 25 NF2 patients. In the NF2 group, 11/25 (44%) presented with IEND below the age- and gender-matched bottom 5% normative reference IEND. In contrast, nearly all (33/34=97%) schwannomatosis patients showed IEND below or on the bottom 5% normative reference. The reduction of IEND in schwannomatosis patients was age-independent. Paired t-test revealed no difference between the NF2-IEND and the corresponding bottom 5% normative reference (P=0.98). By contrast, IEND in the schwannomatosis patients were highly significantly lower than the corresponding 5% normative reference IEND (P<0.0001). In addition, the difference between the IEND of our patients and the 5% lowest normative reference IEND was highly significantly larger in schwannomatosis patients than in NF2 patients (P<0.0001). IEND of our patients did not correlate with neither the presence nor types of germline mutations in neither the NF2 nor the LZTR1 gene. In conclusion, schwannomatosis patients have marked low IEND which provides a major parameter for diagnosis and differential diagnosis. This article is protected by copyright. All rights reserved.
Learn More >We investigated the influence of sleeplessness and number of insomnia symptoms on the probability of recovery from chronic low back pain (LBP), and the possible interplay between sleeplessness and co-occurring musculoskeletal pain on this association.
Learn More >Migraine is highly prevalent and associated with a large socio-economic burden in the United States. Current preventive medications have variable efficacy and their use is often limited by intolerable side effects. Calcitonin gene-related peptide (CGRP) has been identified as an integral part of migraine pathophysiology. There are currently seven CGRP antagonists under investigation, all of which are undergoing or have completed phase 3 clinical trials. Three of the investigated CGRP antagonists are approved for use within and outside of the United States. The trials have resulted in positive efficacy and safety data. The purpose of this review is to evaluate the seven CGRP antagonists and their future place in therapy.
Learn More >Central neuropathic pain (CNP) after spinal cord injury (SCI) is debilitating and immensely impacts the individual. CNP is relatively resistant to treatment administered after it develops, perhaps owing to irreversible pathological processes. Although preemptive treatment may overcome this shortcoming, its administration necessitates screening patients with clinically relevant biomarkers that could predict CNP early post-SCI. The aim was to search for such biomarkers by measuring pro-nociceptive and for the first time, anti-nociceptive indices early post-SCI.Participantswere 47 patients with acute SCI and 20 healthy controls (HC). Pain adaptation, conditioned pain modulation (CPM), pain temporal summation (TSP), windup pain, and allodynia were measured above, at, and below the injury level, at 1.5 months post-SCI. HC were tested at corresponding regions. SCI patients were monitored for CNP emergence and characteristics at 3-4, 6-7, and 24 months post-SCI.CNP prevalence was 57.4%. CNP severity, quality and aggravating factors but not location somewhat changed over 24 months. SCI patients who eventually developed CNP exhibited early, reduced at-level pain adaptation and CPM magnitudes than those who did not. The best predictor for CNP emergence at 3-4 and 7-8 months was at-level pain adaptation with odds ratios of 3.17 and 2.83, respectively (∼77% probability) and a cut-off value with 90% sensitivity. Allodynia and at-level CPM predicted CNP severity at 3-4 and 24 months, respectively.Reduced pain inhibition capacity precedes, and may lead to CNP. At-level pain adaptation is an early CNP biomarker with which individuals at risk can be identify to initiate preemptive treatment.
Learn More >Mu and delta opioid receptors play opposite nociceptive and behavioural roles on nerve-injured mice.
Mu and delta opioid receptors (MOP, DOP) limit pain perception in physiological conditions, but their relative contribution to the manifestations of pathological pain is not completely understood. Here we used a genetic approach to investigate the opioid mechanisms modulating neuropathic pain and its comorbid manifestations.
Learn More >To report evidence of chronic physical illnesses, mental health disorders, and psychological features as potential risk factors for back pain in children, adolescents, and young adults.
Learn More >Oxaliplatin is a widely used chemotherapeutic drug and represents the cornerstone of colorectal cancer therapy, in combination with 5-fluorouracil and folinic acid. As with many chemotherapeutic agents, its use is associated with a number of side effects, ranging from hypersensitivity reactions to haematological dyscrasias. Oxaliplatin also induces acute and chronic peripheral neuropathy. While it is likely that the haematological side effects are associated with its anti-proliferative effects and with the ability to form DNA adducts, the molecular mechanisms underlying peripheral neuropathy and hypersensitivity reactions are poorly understood, and therefore the choice of adequate supportive therapies is largely empirical. Here we show that an acute low dose oxaliplatin application on DRG neurons is able to induce an increase in intracellular calcium that is dependent on the Histamine 1 receptor (H1). Oxaliplatin-induced intracellular calcium rises are blocked by two selective H1 antagonist, as well as by U73122, a PLC inhibitor, and by 2-APB, a non-specific IP receptor blocker. Moreover, expression of the H1 receptor on HEK293 t cells unmasks an oxaliplatin-induced Ca-rise. Last, activation of H1 via either histamine or oxaliplatin activates TRPV1 receptors, a mechanism that has been associated with itch. These data, together with literature data that has shown that anti-histamine agents reduce the incidence of oxaliplatin-induced hypersensitivity, may provide a molecular mechanism of this side effect in oncological patients.
Learn More >Disability in inflammatory bowel disease (IBD) is under-investigated. Models theorize that disability is the result of a disease and its related impairments, limitations, and restrictions. This disablement process can be affected by psychosocial factors. Pain, depression, catastrophizing, and social support are associated with IBD-disability outcomes, but no studies have examined these factors concurrently. This study examined the role of psychosocial factors in the process of IBD disablement within the context of pain. Depressive symptoms, pain catastrophizing, and perceived social support were proposed as mediators in the relationship between pain and pain-related disability in cross-sectional and longitudinal models. Cross-sectionally, the mediation effects of depressive symptoms and pain catastrophizing, but not perceived social support, were significant. Longitudinally, depression was a significant mediator. Depressive symptoms and pain catastrophizing have mechanistic roles in the relationship between IBD patients' pain and pain-related disability and should be targets for intervention.
Learn More >Pain is often the initial complaint for which patients seek medical care presenting both a diagnostic and therapeutic challenge to the primary care provider. The appreciation of pain is not merely the result of abnormal sensory stimulation causing an unpleasant sensation but rather a combination of the recognition of the somatic discomfort in association with an emotional response to that discomfort. The perception of pain and the extent of distress and disability can vary depending on previous experience, cultural background, situational factors, and comorbid psychiatric disease. While acute pain is usually the result of tissue damage, that is not always the case as evidenced by the primary headache disorders. Chronic pain may be the result of an injury, irreversible underlying disease or clinical conditions such as fibromyalgia for which the mechanism remains unclear. Treatment of the underlying cause will usually effect a resolution or improvement in the pain but when the discomfort persists a consultation with a neurologist or pain management specialist should be considered.
Learn More >Pain is a common complaint presented in healthcare, but most epidemiological pain research has focused either on single pain conditions or on the adult population. The aim of this study was to investigate the 2017 consultation prevalence of a wide range of pain conditions in the general population of young people.
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