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Episodic cluster headache is a disabling neurologic disorder that is characterized by daily headache attacks that occur over periods of weeks or months. Galcanezumab, a humanized monoclonal antibody to calcitonin gene-related peptide, may be a preventive treatment for cluster headache.
Learn More >Migraine headache pathophysiology involves trigeminovascular system activation, calcitonin gene-related peptide (CGRP) release and dysfunctional nociceptive transmission. Triptans are 5-HT1B/1D/(1F) receptor agonists that prejunctionally inhibit trigeminal CGRP release, but their vasoconstrictor properties limit their use in migraine patients with cardiovascular disease. In contrast, lasmiditan is a novel antimigraine and selective 5-HT1F receptor agonist devoid of vasoconstrictor properties. On this basis, the present study has investigated the modulation of trigeminal CGRP release by lasmiditan.For this purpose, we have comparatively analysed the inhibition of several components of the trigeminovascular system induced by lasmiditan and sumatriptan through: ex vivo KCl-induced CGRP release from isolated dura mater, trigeminal ganglion and trigeminal nucleus caudalis of mice; and in vivo dural vasodilation in the rat closed-cranial window model induced by endogenous (electrical stimulation, capsaicin) and exogenous CGRP.The ex vivo release of CGRP was similarly inhibited by sumatriptan and lasmiditan in all trigeminovascular system components. In vivo, i.v. lasmiditan or higher doses of sumatriptan significantly attenuated the vasodilatory responses to endogenous CGRP release, but not exogenous CGRP effects. These data suggest that lasmiditan prejunctionally inhibits CGRP release in peripheral and central trigeminal nerve terminals. Since lasmiditan is a lipophilic drug that crosses the blood-brain barrier, additional central sites of action remain to be determined.
Learn More >We explore factors that may have contributed to differences in treatment-emergent adverse events in the phase 2 and phase 3 lasmiditan clinical trials.
Learn More >There is a significant unmet need for novel, effective, and well-tolerated acute migraine treatments. Remote electrical neuromodulation (REN) is a non-pharmacological, non-invasive, acute migraine treatment that stimulates upper arm peripheral nerves to induce conditioned pain modulation – an endogenous analgesic mechanism in which a conditioning stimulation inhibits pain in remote body regions. This review presents the method of action and the clinical data of REN and discusses its potential patient benefits. The clinically meaningful efficacy, together with a very favorable safety profile, suggests that REN may offer a promising alternative for the acute treatment of migraine and could be considered first-line treatment in some patients.
Learn More >To investigate the sensitivity and specificity of the TMD pain screener in a headache population.
Learn More >We explored the atypical functional connectivity (FC) between the anterior cingulate cortex (ACC) and other brain areas in rats subjected to repeated meningeal nociception. The rat model was established by infusing an inflammatory soup (IS) through supradural catheters in conscious rats. Rats were subdivided according to the frequency of the IS infusions. FC analysis seeded on the ACC was performed on rats 21 days after IS infusion. Glyceryl trinitrate was injected following baseline scanning in the low-frequency IS (LF-IS) group and magnetic resonance imaging (MRI) data were acquired 1 hour after the injection. The rats exhibited nociceptive behavior after high-frequency IS (HF-IS) infusion. The ACC showed increased FC with the cerebellum in the IS groups. The medulla showed increased FC with the ACC in the ictal period in the LF-IS rats. Several areas showed increased FC with the ACC in the HF-IS group, including the pontine tegmentum, midbrain, thalamus, corpus callosum, hippocampus, and retrosplenial, visual, sensory, and motor cortices. This study indicated that the medulla participates in the early stage of a migraine attack and may be associated with the initiation of migraine. Sensitization of the trigeminal nociceptive pathway might contribute to the cutaneous allodynia seen in chronic migraine. Brain areas important for memory function may be related to the chronification of migraine. Electrophysiological studies should examine those migraine-related areas and provide new targets for migraine treatment and prevention.
Learn More >To evaluate the possible relationship between sleep disturbances and primary headaches.
Learn More >Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist under investigation for acute treatment of migraine.
Learn More >: The neuropeptide calcitonin gene-related peptide (CGRP) is recognized as a critical player in migraine pathophysiology. Excitement has grown regarding CGRP because of the development and clinical testing of drugs targeting CGRP or its receptor. While these drugs alleviate migraine symptoms in half of patients, the remaining unresponsive half of this population creates an impetus to address unanswered questions that exist in this field.: We describe the role of CGRP in migraine pathophysiology and CGRP-targeted therapeutics currently under development and in use. We also discuss how a second CGRP receptor may provide a new therapeutic target.: CGRP targeting drugs have shown a remarkable safety profile. We speculate that this may reflect the redundancy of peptides within the CGRP family and a second CGRP receptor that may compensate for reduced CGRP activity. Furthermore, we propose that an inherent safety feature of peptide-blocking antibodies is attributed to the fundamental nature of peptide release, which occurs as a large bolus in short bursts of volume transmission. These facts support the development of more refined CGRP therapeutic drugs, as well as drugs that target other neuropeptides. We believe that the future of migraine research is bright with exciting advances on the horizon.
Learn More >There is a major unmet need to develop new therapies for migraine. We have previously demonstrated the therapeutic potential of the acid sensing ion channel (ASIC) blockade in migraine, via an ASIC1 mechanism. ASIC3 is expressed in the trigeminal ganglion and its response is potentiated by nitric oxide that can trigger migraine attacks in patients, and thus we sought to explore the potential therapeutic effect of ASIC3 blockade in migraine.
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