Browse by Audience
Presentation of pooled analysis of safety data for fremanezumab in patients with chronic (CM) or episodic migraine (EM) from 4 placebo-controlled phase 2b and phase 3 studies.
Learn More >Burning mouth syndrome (BMS) is a chronic orofacial pain disorder of unknown cause. It is more common in peri- and postmenopausal women, and sex hormone dysregulation is believed to be an important causative factor. Psychosocial events often trigger or exacerbate symptoms, and persons with BMS appear to be predisposed toward anxiety and depression. Atrophy of small nerve fibers in the tongue epithelium has been reported, and potential neuropathic mechanisms for BMS are now widely investigated. Historically, BMS was thought to comprise endocrinological, psychosocial, and neuropathic components. Neuroprotective steroids and glial cell line-derived neurotrophic factor family ligands may have pivotal roles in the peripheral mechanisms associated with atrophy of small nerve fibers. Denervation of chorda tympani nerve fibers that innervate fungiform buds leads to alternative trigeminal innervation, which results in dysgeusia and burning pain when eating hot foods. With regard to the central mechanism of BMS, depletion of neuroprotective steroids alters the brain network related mood and pain modulation. Peripheral mechanistic studies support the use of topical clonazepam and capsaicin for the management of BMS, and some evidence supports the use of cognitive behavioral therapy. Hormone replacement therapy may address the causes of BMS, although adverse effects prevent its use as a first-line treatment. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) may have important benefits, and well-designed controlled studies are expected. Other treatment options to be investigated include brain stimulation and TSPO (translocator protein 18 KDa) ligands. This article is protected by copyright. All rights reserved.
Learn More >To examine dorsal root ganglia and proximal nerve segments in patients carrying the Fabry-related GLA-gene variant p.D313Y in comparison to patients with classical Fabry mutations and healthy controls by morphometric and functional magnetic resonance neurography.
Learn More >Following injury to the peripheral nervous system (PNS), microglia in the spinal dorsal horn (SDH) become activated and contribute to the development of local neuro-inflammation, which may regulate neuropathic pain processing. The molecular mechanisms that control microglial activation and its effects on neuropathic pain remain incompletely understood. We deleted the gene encoding the plasma membrane receptor, LDL Receptor-related Protein-1 (LRP1), conditionally in microglia using two distinct promoter-Cre recombinase systems in mice. LRP1 deletion in microglia blocked development of tactile allodynia, a neuropathic pain-related behavior, after partial sciatic nerve ligation (PNL). LRP1 deletion also substantially attenuated microglial activation and pro-inflammatory cytokine expression in the SDH following PNL. Because LRP1 shedding from microglial plasma membranes generates a highly pro-inflammatory soluble product, we demonstrated that factors which activate spinal cord microglia, including lipopolysaccharide (LPS) and colony-stimulating factor-1, promote LRP1 shedding. Proteinases known to mediate LRP1 shedding, including ADAM10 and ADAM17, were expressed at increased levels in the SDH after PNL. Furthermore, LRP1-deficient microglia in cell culture expressed significantly decreased levels of interleukin-1β and interleukin-6 when treated with LPS. We conclude that in the SDH, microglial LRP1 plays an important role in establishing and/or amplifying local neuro-inflammation and neuropathic pain following PNS injury. The responsible mechanism most likely involves proteolytic release of LRP1 from the plasma membrane to generate a soluble product that functions similarly to pro-inflammatory cytokines in mediating crosstalk between cells in the SDH and in regulating neuropathic pain.
Learn More >Knee arthroplasty (KA) is an effective surgical procedure. However, clinical studies suggest that a considerable number of patients continue to experience substantial pain and functional loss following surgical recovery. We aimed to estimate pain and function outcome trajectory types for persons undergoing KA, and to determine the relationship between pain and function trajectory types, and pre-surgery predictors of trajectory types.
Learn More >Musculoskeletal (MSK) pain represents a considerable worldwide healthcare burden. This study aimed to gain consensus from practitioners who work with MSK pain patients, on the most appropriate primary care treatment options for subgroups of patients based on prognostic risk of persistent disabling pain. Agreement was sought on treatment options for the five most common MSK pain presentations: back, neck, knee, shoulder and multisite pain, across three risk subgroups: low, medium and high.
Learn More >Migraine is the most common of all neurological disorders. A breakthrough in migraine treatment emerged in the early nineties with the introduction of 5-HT1B/D receptor agonists called triptans. Triptans are used as the standard of care for acute migraine; however, they have significant limitations such as incomplete and inconsistent pain relief, high rates of headache recurrence, class- specific side effects and cardiovascular contraindications. First- and second-generation calcitonin gene-related peptide (CGRP) receptor antagonists, namely gepants, is a class of drugs primarily developed for the acute treatment of migraine. CGRP is the most evaluated target for migraine treatments that are in development. Areas covered: This article reviews the available data for first- and second-generation CGRP receptor antagonists, the role of CGRPs in human physiology and migraine pathophysiology and the possible mechanism of action and safety of CGRP targeted drugs. Expert opinion: Available data suggest that second generation of gepants has clinical efficacy similar to triptans and lasmiditan (5-HT1F receptor agonist) and has improved tolerability. Future studies will assess their safety, especially in specific populations such as patients with cardiovascular disease and pregnant women.
Learn More >Approximately 10% of pediatric patients have recurrent headaches, with migraine being the most common headache type. If untreated, migraine may progress to status migrainosus, a debilitating condition of prolonged duration, high pain severity, and significant disability. There is high variability in the treatment of status migrainosus including medications used and treatment setting, which may occur in the emergency room, as an inpatient admission, or, less often, in an outpatient infusion center. The paucity of research on the treatment of status migrainosus is a limitation to treatment effectiveness.
Learn More >Despite the serious side effects, analgesics acting on opioid receptors are still considered the best way to get antinociception. Matrix metalloproteinases, a large family of zinc-dependent proteases implicated in many pathological conditions, such as diabetes and osteoarthritis, are also involved in inflammation and pain. Methodology & results: Looking for evidence of possible interactions of opioid pathways and inflammation mediators, molecular modeling studies of a series of recently developed μ-opioid receptor benzomorphanic agonists together with biological data on pain and inflammation molecular targets, allowed us to hypothesize a possible correlation between μ-opioid receptor system and MMP-9.
Learn More >Migraine is a primary headache disorder and one of the most common and disabling neurological diseases worldwide. Genome-wide association studies have identified ≈40 genetic loci associated with migraine. How these and other genetic findings are used to expand our knowledge on the pathophysiological mechanism of common migraine and rare migraine variants will be discussed.
Learn More >