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Nonsteroidal anti-inflammatory drugs are widely used for migraine, but gastrointestinal tolerability limits use. We previously reported results from the first treatment period of this 2-period, randomized, controlled study comparing DFN-15-an oral, ready-made liquid solution of a selective cyclo-oxygenase-2 inhibitor celecoxib-with placebo for the acute treatment of a moderate-severe migraine attack. Herein, we report the effects of treatment for the second treatment period.
Learn More >Headaches are common in primary care. The diagnosis is made by a careful history and physical examination. Imaging is generally not warranted. Several general principles underlie the acute treatment of headache: early initiation of therapy and adequate dosing at first dose. Careful attention to avoiding too frequent administration of acute therapy is important to avoid medication overuse headaches. Opioids should always be avoided. Preventive treatment is indicated for frequent headaches. Successful treatment entails low-dose medication with careful titration and monitoring of headache frequency. Behavioral strategies are important and should be part of any comprehensive headache management plan.
Learn More >The development of small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists (gepants) and of monoclonal antibodies targeting the CGRP system has been a major advance in the management of migraine. In the randomized controlled trials before regulatory approval, the safety of these anti-CGRP migraine therapeutics was considered favorable and to stay within the expected profile. Post-approval real-world surveys reveal, however, constipation to be a major adverse event which may affect more than 50% of patients treated with erenumab (an antibody targeting the CGRP receptor), fremanezumab or galcanezumab (antibodies targeting CGRP). In this review article we address the question whether constipation caused by inhibition of CGRP signaling can be mechanistically deduced from the known pharmacological actions and pathophysiological implications of CGRP in the digestive tract. CGRP in the gut is expressed by two distinct neuronal populations: extrinsic primary afferent nerve fibers and distinct neurons of the intrinsic enteric nervous system. In particular, CGRP is a major messenger of enteric sensory neurons which in response to mucosal stimulation activate both ascending excitatory and descending inhibitory neuronal pathways that enable propulsive (peristaltic) motor activity to take place. In addition, CGRP is able to stimulate ion and water secretion into the intestinal lumen. The motor-stimulating and prosecretory actions of CGRP combine in accelerating intestinal transit, an activity profile that has been confirmed by the ability of CGRP to induce diarrhea in mice, dogs and humans. We therefore conclude that the constipation elicited by antibodies targeting CGRP or its receptor results from interference with the physiological function of CGRP in the small and large intestine in which it contributes to the maintenance of peristaltic motor activity, ion and water secretion and intestinal transit.
Learn More >Calcitonin gene-related peptide (CGRP) dilates cranial arteries and triggers headache. The CGRP signaling pathway is partly dependent on activation of ATP-sensitive potassium (K ) channels. Here, we investigated the effect of the K channel blocker glibenclamide on CGRP-induced headache and vascular changes in healthy volunteers.
Learn More >The aim of this observational study was to describe social support and patterns of attachment among patients with migraine. We hypothesized that in comparison to the general population, insecure attachment is overrepresented in migraine patients, and that these patients have less social support. We also aimed to study the specific relationship between attachment and social support. We hypothesized that patients with an insecure attachment style have less social support than patients with a secure attachment style. A total of 101 consecutive patients (88.1% women) aged between 25 and 60 (average age = 41.4) were recruited at the Specialized Center for the Consultation of Primary Headaches at the Regional University Hospital Center of Besançon (France). Migraine impact and disability were evaluated using the Headache Impact Test (HIT-6) questionnaire and Migraine Disability Assessment (MIDAS) questionnaire. Patients also completed several self-administered psychological questionnaires in their validated French versions: the Medical Outcome Survey 36-Item Short-Form Health Survey, the Cungi Scale, the State-Trait Anxiety Inventory, the Beck Depression Inventory, the Relationship Scales Questionnaire and the Sarason's Social Support Questionnaire. The distribution of attachment profiles was different from that of the general population, with an overrepresentation of insecure attachment styles ( = 0.018). Our study showed that migraine patients had less social support than the general population, both in terms of the number of people providing support ( = 0.002) and the level of satisfaction concerning this social support (p = 0.000). We also found that neither the number of available persons score nor the satisfaction score were statistically different between the four attachment categories ( = 0.49). Patient's attachment style and social support influence the patient-doctor relationship, the therapeutic alliance and health behaviors such as treatment adherence. Based on the data we obtained, we developed applications in patient care for people with particular attachment styles and low social support. A treatment plan adapted to the patient's attachment profile should be created to develop "precision medicine" using a personalized approach to the doctor-patient relationship. We would also recommend encouraging patients to participate in support groups, in order to strengthen their attachment systems and gain social support. https://clinicaltrials.gov/ct2/show/NCT03577548, identifier NCT03577548.
Learn More >In a phase 3 study, galcanezumab significantly reduced the frequency of episodic cluster headache attacks across weeks 1-3 (primary endpoint) compared with placebo. However, multiple pain dimensions may contribute to the total burden of episodic cluster headache pain. This post hoc analysis assessed the impact of galcanezumab on the total pain burden of episodic cluster headache using a composite measure.
Learn More >The COVID-19 pandemic has spurred a hasty transition to virtual care but also an abundance of new literature highlighting telehealth's capabilities and limitations for various healthcare applications. In this review, we aim to narrate the current state of the literature on telehealth applied to migraine care. First, telemedicine in the context of non-acute headache management has been shown to produce non-inferior patient outcomes when compared to traditional face-to-face appointments. The assignment of patients to telehealth appointments should be made after referring more urgent cases to dedicated in-person clinics. During the virtual appointment, physicians can ask their patients about the "3 F's" in order to perform a thorough assessment of their headaches: frequency of headache days, frequency of acute medication usage and functional impairment. Clinical assessment scores that have been studied and deemed feasible for telemedicine, safe and efficient include the HIT-6, VAS and MIDAS scores. Although MIDAS was found to be redundant and inadequate to use on a daily basis, we suggest that it can be useful in periodic remote follow-up appointments. Additionally, several mobile health apps have been studied including Migraine Buddy, Migraine Coach and Migraine Monitor. All of these are appropriate for use in telemedicine when combined with an adequate trial period with Migraine Buddy being rated the highest, as it captures the most detailed clinical picture. High satisfaction rates have been reported for virtual headache management which were shown to be equal to in-person consults. These are based on patients' perceived increase in convenience due to avoided travel time, less disruption of their daily routine and feeling more comfortable in the environment of their choice. Despite this, limitations such as technological knowledge, access to videoconferencing modalities and having a more impersonal consultation with the physician may hinder some patients from adopting this service.
Learn More >Migraine is a medical condition with a severe recursive headache. The activation of the trigeminovascular system is an important mechanism. The neuropeptide calcitonin gene-related peptide (CGRP) plays a crucial role in the pathogenesis of migraine. Several other neuropeptides are also involved; however, their roles in migraine remain unclear. In this study, using a rat model of migraine induced by electrical stimulation of the trigeminal ganglia (TG) and an improved version induced with repeated stimulation, we observed the dynamic changes of these peptides in TG and blood. We demonstrated that the expression of CGRP, pituitary adenylate cyclase activating polypeptide (PACAP), neuropeptide Y (NPY), vasoactive intestinal peptide, and nociceptin in TG was significantly elevated and peaked at different time points after a single stimulation. Their levels in the blood plasma were significantly increased at 12 h after stimulation. The peptides were further elevated with repeated stimulation. The improved rat model of migraine with repeated stimulation of TG resulted in a more pronounced elevation of CGRP, PACAP, and NPY. Thus, the dynamic changes in neuropeptides after stimulation suggest that these neuropeptides may play an important role in the pathogenesis of migraine. Additionally, the migraine model with repetitive stimulation would be a novel model for future research.
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