The journal of headache and pain
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5-Hydroxytryptamine (5-HT) receptors 1B, 1D and 1F have key roles in migraine pharmacotherapy. Selective agonists targeting these receptors, such as triptans and ditans, are effective in aborting acute migraine attacks and inhibit the in vivo release of calcitonin gene-related peptide (CGRP) in human and animal models. The study aimed to examine the localization, genetic expression and functional aspects of 5- HT1B/1D/1F receptors in the trigeminal system in order to further understand the molecular sites of action of triptans (5-HT1B/1D) and ditans (5-HT1F). ⋯ This study reveals the presence of a subgroup of C-fibres that store 5-HT. The data shows high expression of 5-HT1B/1D receptors and suggests that the 5-HT1F receptor is a relatively unlikely target in the rat TG. Furthermore, Lasmiditan works as a partial agonist on 5-HT1B/1D receptors in clinically relevant dose regiments.
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Central sensitization is an important pathophysiological mechanism of chronic migraine (CM), and microglia activation in trigeminocervical complex (TCC) contributes to the development of central sensitization. Emerging evidence implicates that blocking sphingosine-1-phosphate receptor 1 (S1PR1) can relieve the development of chronic pain and inhibit the activation of microglia. However, it is unclear whether S1PR1 is involved in the central sensitization of CM. Therefore, the purpose of this study is to explore the role of S1PR1 and its downstream signal transducers and activators of transcription 3 (STAT3) signaling pathway in the CM, mainly in inflammation. ⋯ Our results indicate that inhibiting S1PR1 signal could alleviate central sensitization and inhibit microglia activity caused by chronic NTG administration via STAT3 signal pathway, which provide a new clue for the clinical treatment of CM.
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Randomized Controlled Trial
Early onset of efficacy with fremanezumab in patients with episodic and chronic migraine: subanalysis of two phase 2b/3 trials in Japanese and Korean patients.
Early onset of action has become recognized as an important efficacy feature of preventive migraine treatment, which can help overcome adherence issues commonly associated with older medications. Preventive treatments that target the calcitonin gene-related peptide (CGRP) or the CGRP receptor have been previously shown to provide early onset of action. ⋯ These results suggest that fremanezumab has an early onset of action, as noted in previous post hoc analyses of anti-CGRP monoclonal antibodies.
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Randomized Controlled Trial
Eptinezumab treatment initiated during a migraine attack is associated with meaningful improvement in patient-reported outcome measures: secondary results from the randomized controlled RELIEF study.
Demonstrating therapeutic value from the patient perspective is important in patient-centered migraine management. The objective of this study was to investigate the impact of eptinezumab, a preventive migraine treatment, on patient-reported headache impact, acute medication optimization, and perception of disease change when initiated during a migraine attack. ⋯ When administered during a migraine attack, eptinezumab significantly improved patient-reported outcomes after 4 weeks compared with placebo, with particularly pronounced effects in patients reporting headache pain freedom at 2 h after infusion start.
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Randomized Controlled Trial
Patient-reported outcomes, health-related quality of life, and acute medication use in patients with a ≥ 75% response to eptinezumab: subgroup pooled analysis of the PROMISE trials.
PROMISE-1 and PROMISE-2 evaluated the preventive efficacy, tolerability, and safety of eptinezumab, a calcitonin gene-related peptide-targeted monoclonal antibody, in adults with episodic (EM) and chronic migraine (CM), finding significant reductions in migraine frequency. This post hoc analysis compared patient-reported outcomes (PROs), health-related quality of life (HRQoL) and acute medication use in patients with a ≥ 75% migraine responder rate (MRR) after treatment with eptinezumab to patients with a ≥ 50- < 75% MRR. ⋯ Eptinezumab treatment induced a ≥ 75% MRR over wks1-12 in the majority of patients. This patient subgroup reported substantial improvements in PROs associated with headache-related life impact and HRQoL, and reductions in acute headache medication use, which were more marked than those in the ≥ 50-< 75% responders. This study supports the clinical meaningfulness of ≥ 75% MRR for patients with either EM or CM.