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- Edvinsson, Lars
(författare)
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The CGRP Pathway in Migraine as a Viable Target for Therapies
- 2018
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Ingår i: Headache. - : Wiley. - 0017-8748. ; 58, s. 33-47
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Tidskriftsartikel (refereegranskat)abstract
- The neuropeptide calcitonin gene-related peptide is well established as a key player in the pathogenesis of migraine. Clinical studies show calcitonin gene-related peptide levels correlate with migraine attacks, and decreases in this neuropeptide can indicate antimigraine therapy effectiveness. Research has revealed a wide distribution of expression sites for calcitonin gene-related peptide in the central and peripheral nervous system. Of these, the calcitonin gene-related peptide receptor, which binds calcitonin gene-related peptide with high affinity, has attracted growing interest as a viable target for antimigraine therapies. An incentive to pursue such research is the continuing unmet medical need of patients. Triptans have offered some clinical benefit, but many patients do not respond and these drugs have important safety considerations. Initial calcitonin gene-related peptide-focused research led to development of the “gepant” small-molecule calcitonin gene-related peptide receptor blockers. Positive efficacy reports concerning the gepants have been tempered by safety findings which led to the discontinuation of some of these agents. Currently, there is considerable excitement regarding monoclonal antibodies against calcitonin gene-related peptide (eptinezumab, galcanezumab, fremanezumab) and the calcitonin gene-related peptide receptor (erenumab). To date, these monoclonal antibodies have shown promising efficacy in clinical trials, with no major safety concerns. If ongoing long-term studies show that their efficacy can be maintained, this may herald a new era for effective antimigraine therapies.
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| 2. |
- Edvinsson, Lars
(författare)
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The Journey to Establish CGRP as a Migraine Target: A Retrospective View.
- 2015
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Ingår i: Headache. - : Wiley. - 1526-4610. ; 55:9, s. 1249-1255
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Tidskriftsartikel (refereegranskat)abstract
- In this retrospective, Dr. Lars Edvinsson recounts early steps and milestones in our understanding of the neuropeptide calcitonin gene-related peptide (CGRP) in the trigeminovascular system and its role in migraine. The discovery of the presence and function of CGRP and other neuropeptides in the cerebral vasculature and its sensory innervation is described. He relates the seminal finding that CGRP is uniquely released during migraine and the journey to develop blockers of CGRP effects. Now, over 30 years since its discovery, CGRP has become the target for a number of promising novel treatments for migraine patients.
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| 3. |
- Edvinsson, Lars
(författare)
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The Trigeminovascular Pathway : Role of CGRP and CGRP Receptors in Migraine
- 2017
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Ingår i: Headache. - : Wiley. - 0017-8748. ; 57, s. 47-55
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Forskningsöversikt (refereegranskat)abstract
- The trigeminal ganglion plays a key role in primary headache pathophysiology. Calcitonin gene-related peptide (CGRP) and CGRP receptors are expressed in trigeminal neurons that form C-fibers and A-fibers, respectively. In acute migraine and cluster headache attacks, there is release of CGRP into the cranial venous outflow. In addition, intravenous CGRP can induce migraine-like symptoms in migraine patients. These findings led to the development of anti-migraine therapies that inhibit CGRP action. Currently, CGRP receptor antagonists, the gepants, and monoclonal antibodies towards CGRP and the CGRP receptor are all showing positive relief of acute and chronic migraine in clinical trials. However, there is still much to learn about the role of CGRP and CGRP receptors in headache pathophysiology, the critical anatomical sites, peripheral or central, of anti-CGRP agents, and the potential involvement of CGRP-related peptides and receptors. This review provides a brief history of the discovery of the role of CGRP in migraine and highlights current progress in understanding the complexity of the trigeminovascular pathway and its peptide transmitters.
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| 6. |
- Ikoma, Tomoko, et al.
(författare)
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Effects of Low-Intensity Contractions of Different Craniofacial Muscles in Healthy Participants : An Experimental Cross-Over Study
- 2018
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Ingår i: Headache. - : John Wiley & Sons. - 0017-8748 .- 1526-4610. ; 58:4, s. 559-569
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Tidskriftsartikel (refereegranskat)abstract
- Objective.-Repetitive jaw-muscle activity characterized by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible, ie, bruxism, is traditionally linked to pain and unpleasantness in the active muscles. The aim of this study was to investigate the effects of standardized craniofacial muscle contractions on self-reported symptoms. Methods.-Sixteen healthy volunteers performed six 5-minute bouts of 20% maximal voluntary contraction task of the jaw-closing (Jaw), the orbicularis-oris (O-oris), and the orbicularis-oculi (O-oculi) muscles. Participants rated their perceived pain, unpleasantness, fatigue, and mental stress levels before, during, and after the contraction tasks on 0-10 Numeric Rating Scales (NRS). Each muscle contraction task (= 1 session) was separated by at least 1 week and the order of the sessions was randomized in each subject. Results.-All muscle contraction tasks evoked significant increases in NRS scores of pain (mean +/- SD: Jaw; 3.8 +/- 2.7, O-oris; 1.9 +/- 2.2, O-oculi; 1.4 +/- 1.3, P < .014), unpleasantness (Jaw; 4.1 +/- 2.5, O-oris; 2.1 +/- 1.9, O-oculi; 2.9 +/- 1.8, P<.001), fatigue (Jaw; 5.8 +/- 2.0, O-oris; 3.2 +/- 2.3, O-oculi; 3.6 +/- 1.9, P<.001), and mental stress (Jaw; 4.1 +/- 2.1, O-oris; 2.2 +/- 2.7, O-oculi; 2.9 +/- 2.2, P<.001). The Jaw contractions were associated with higher NRS scores compared with the O-oris and the O-oculi contractions (P<.005) without differences between the O-oris and the O-oculi (P>.063). All symptoms disappeared within 1 day (P>.469). Conclusions.-The results showed that submaximal static contractions of different craniofacial muscle groups could evoke transient, mild to moderate levels of muscle pain and fatigue and increased stress scores. The fatigue resistance may differ between different muscle groups. Further studies are warranted to better understand the contribution of specific craniofacial muscle groups for the characteristic presentation of musculoskeletal pain conditions in the head.
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| 8. |
- Lebwohl, Benjamin, et al.
(författare)
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Risk of Headache-Related Healthcare Visits in Patients With Celiac Disease : A Population-Based Observational Study
- 2016
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Ingår i: Headache. - Hoboken, USA : Wiley-Blackwell. - 0017-8748 .- 1526-4610. ; 56:5, s. 849-858
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Patients with celiac disease (CD) are reported to be at increased risk for headaches, though large studies are lacking. We aimed to examine the risk of headache-related healthcare encounters in patients with CD in a nationwide population-based setting.Methods: In this population-based retrospective cohort study, we searched all (n = 28) pathology departments in Sweden and identified patients with CD based on the presence of villous atrophy (VA). Each patient was matched to up to 5 controls, by age, gender, calendar period, and region. Using Cox proportional hazards, we tested for an association between CD and subsequent headache-related visit. We also tested this association for those with intestinal inflammation but normal villi, and subjects with positive CD serologies but normal histology.Results: Among 28,638 patients with CD and 143,126 controls, headache-related visit occurred in 1,337 (4.7%) and 4,102 (2.9%), respectively. The incidence of headache-related visit was 423 per 100,000 person-years in CD patients and 254 per 100,000 person-years in controls (HR 1.66; 95% CI 1.56-1.77; P < .0001). Individuals having inflammation without VA on small intestinal biopsy (n = 12,898; HR 2.08; 95% CI 1.90-2.27; P < .0001) and those with normal mucosa but positive CD serology (n = 3,617; HR 1.83; 95% CI 1.57-2.12; P < .0001) were also at increased risk for headache-related visit.Conclusions: In this population-based study we found a significantly increased risk of headache-related visits in patients with CD; this increase was also present in patients with intestinal inflammation and those with positive CD serology but with normal mucosal architecture on small bowel biopsy. Though limited by surveillance bias, this study indicates that headache-related visits are more common in these populations.
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