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Erenumab patient characteristics, medication adherence, and treatment patterns in the United States.
To describe patient characteristics, adherence, and treatment patterns, among adult migraine patients in the United States prescribed erenumab.
Learn More >To date, two randomized, controlled studies support the use of candesartan for migraine prophylaxis but with limited external validity. We aim to evaluate the effectiveness and tolerability of candesartan in clinical practice and to explore predictors of patient response. Retrospective cohort study including all patients with migraine who received candesartan between April 2008-February 2019. The primary endpoint was the number of monthly headache days during weeks 8-12 of treatment compared to baseline. Additionally, we evaluated the frequency during weeks 20-24. We analysed the percentage of patients with 50% and 75% response rates and the retention rates after three and 6 months of treatment. 120/4121 patients were eligible, aged 45.9 [11.5]; 100 (83.3%) female. Eighty-four patients (70%) had chronic migraine and 53 (42.7%) had medication-overuse headache. The median number of prior prophylactics was 3 (Inter-quartile range 2-5). At baseline, patients had 20.5 ± 8.5 headache days per month, decreasing 4.3 ± 8.4 days by 3 months (weeks 12-16) and by 4.7 ± 8.7 days by 6 months (paired Student's t-test, p < 0.001). The percentage of patients with a 50% response was 32.5% at 3 months and 31.7% at 6 months, while the retention rate was 85.0% and 58.3%. The number of prior treatments (Odds ratio 0.79, 95% CI 0.64-0.97) and the presence of daily headache (Odds ratio 0.39, 95% CI 0.16-0.97) were associated with a lower probability of response. Candesartan showed beneficial effects in the preventive treatment of migraine in clinical practice, including patients with chronic migraine, medication-overuse headache and resistance to prior prophylactics.
Learn More >Intrathecal (IT) drug therapy has been established as an effective treatment option for patients with chronic pain of malignant or non-malignant origin, with an established safety profile and fewer adverse effects compared to oral or parenteral pain medications. Morphine (a μ-opioid receptor agonist) and ziconotide (a non-opioid calcium channel antagonist) are the only IT agents approved by the US Food and Drug Administration for the treatment of chronic pain. Although both are considered first-line IT therapies, each drug has unique properties and considerations. Areas Covered: This review will evaluate the pivotal trials that established the use of morphine and ziconotide as first-line IT therapy for patients with chronic pain, as well as safety and efficacy data generated from various retrospective and prospective studies. Expert Opinion: Morphine and ziconotide are effective IT therapies for patients with chronic malignant or non-malignant pain that is refractory to other interventions. IT ziconotide is recommended as first-line therapy due to its efficacy and avoidance of many adverse effects commonly associated with opioids. The use of IT morphine is also considered first-line; however, the risks of respiratory depression, withdrawal with drug discontinuation or pump malfunction, and the development of tolerance require careful patient selection and management.
Learn More >The efficacy of triptans as the main acute treatment strategy for migraine headache at the population-wide level needs to be understood to inform clinical decision-making. We summarise key trends in triptan use using more than 25 years of Danish nationwide data.
Learn More >Opioid abuse is a chronic disorder likely involving stable neuroplastic modifications. While a number of molecules contributing to these changes have been identified, the broader spectrum of genes and gene networks that are affected by repeated opioid administration remain understudied.
Learn More >Opioid and GABA receptors are both located in central nociceptive pathways, and compounds that activate these receptors have pain-relieving properties. To date, the interactive effects of concurrent administration of these compounds in preclinical models of pain-like behaviors have not been assessed.
Learn More >Interleukin-4 (IL-4) is an anti-inflammatory cytokine, which can be protective in inflammatory and neurological disorders, and can alleviate pain. Classically, IL-4 diminishes pain by blocking the production of pro-inflammatory cytokines. Here, we uncovered that IL-4 induces acute antinociception by IL-4 receptor α (IL-4Rα)-dependent release of opioid peptides from M1 macrophages at injured nerves. As a model of pathological pain we used a chronic constriction injury (CCI) of the sciatic nerve in male mice. A single application of IL-4 at the injured nerves (14 days following CCI) attenuated mechanical hypersensitivity evaluated by von Frey filaments, which was reversed by co-injected antibody to IL-4Rα, antibodies to opioid peptides such as Met-enkephalin (ENK), β-endorphin and dynorphin A 1-17, and selective antagonists of δ-, µ- and κ-opioid receptors. Injured nerves were predominately infiltrated by pro-inflammatory M1 macrophages and IL-4 did not change their numbers or the phenotype, assessed by flow cytometry and qRT-PCR, respectively. Macrophages isolated from damaged nerves by immunomagnetic separation and stimulated with IL-4 dose-dependently secreted all three opioid peptides measured by immunoassays. The IL-4-induced release of ENK was diminished by IL-4Rα antibody, intracellular Ca chelator, and inhibitors of protein kinase A (PKA), phosphoinositide 3-kinase (PI3K), and ryanodine receptors. Together, we identified a new opioid mechanism underlying the IL-4-induced antinociception that involves PKA-, PI3K-, ryanodine receptor-, and intracellular Ca-mediated release from M1 macrophages of opioid peptides, which activate peripheral opioid receptors in injured tissue.Interleukin-4 (IL-4) is an anti-inflammatory cytokine, which can ameliorate pain. The IL-4-mediated effects are considered to mostly result from the inhibition of the production of pro-inflammatory mediators (e.g., IL-1β, tumor necrosis factor, prostaglandin E2). Here, we found that IL-4 injected at the injured nerves attenuates pain by releasing opioid peptides from the infiltrating macrophages in mice. The opioids were secreted by IL-4 in the intracellular Ca-dependent manner and activated local peripheral opioid receptors. These actions represent a novel mode of IL-4 action, since its releasing properties have not been so far reported. Importantly, our findings suggest that the IL-4-opioid system should be targeted in the peripheral damaged tissue, since this can be devoid of central and systemic side effects.
Learn More >Migraine is highly prevalent and is the sixth leading cause worldwide for years lost to disability. Therapeutic options specifically targeting migraine are limited, and delta opioid receptor (DOP) agonists were recently identified as a promising pharmacotherapy. The mechanisms by which DOPs regulate migraine are currently unclear. Calcitonin gene- related peptide (CGRP) has been identified as an endogenous migraine trigger and plays a critical role in migraine initiation and susceptibility. The aim of this study was to determine the behavioral effects of DOP agonists on the development of chronic migraine-associated pain, and to investigate DOP co-expression with CGRP and CGRP receptor in the trigeminal system. Chronic migraine-associated pain was induced in mice through repeated intermittent injection of the known human migraine trigger, nitroglycerin. Chronic nitroglycerin resulted in severe chronic cephalic allodynia which was prevented with co-treatment of the DOP-selective agonist, SNC80. In addition, a corresponding increase in CGRP expression in the trigeminal ganglia and trigeminal nucleus caudalis was observed after chronic nitroglycerin, an augmentation that was blocked by SNC80. Moreover, DOP was also upregulated in these head pain-processing regions following the chronic migraine model. Immunohistochemical analysis of the trigeminal ganglia revealed co-expression of DOP with CGRP as well as with a primary component of the CGRP receptor, RAMP1. In the trigeminal nucleus caudalis, DOP was not co-expressed with CGRP but was highly co-expressed with RAMP1 and calcitonin receptor like receptor. These results suggest that DOP agonists inhibit migraine-associated pain by attenuating CGRP release and inhibiting pro-nociceptive signaling of the CGRP receptor.
Learn More >Monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor are a key achievement in the field of migraine prevention, being the first migraine-specific preventatives. Several characteristics distinguish monoclonal antibodies targeting the CGRP pathway from the previously available drug classes for migraine prevention, including their specificity, their monthly or quarterly subcutaneous administration, and their rapid onset of action.
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