Calcitonin Gene-Related Peptide in Tension-Type Headache

In the last 10 years there has been increasing interest in the role of calcitonin gene-related peptide (CGRP) in primary headaches. Tension-type headache is one of the most common and important types of primary headaches, and ongoing nociception from myofascial tissues may play an important role in the pathophysiology of this disorder. CGRP sensory fibers are preferentially located in the walls of arteries, and nerve fibers containing CGRP accompany small blood vessels in human cranial muscles. It is well established that nociception may lead to release of CGRP from sensory nerve endings and from central terminals of sensory afferents into the spinal cord. It has also been shown that density of CGRP fibers around arteries is increased in persistently inflamed muscle. These findings indicate that ongoing activity in sensory neurons in the cranial muscles may be reflected in changes of plasma levels of neuropeptides in patients with chronic tension-type headache. To explore the possible role of CGRP in tensiontype headache, plasma levels of CGRP were measured in patients with chronic tension-type headache. This study showed that plasma levels of CGRP are normal in patients and unrelated to headache state. However, the findings of normal plasma levels of CGRP do not exclude the possibility that abnormalities of this neuropeptide at the neuronal or peripheral (pericranial muscles) levels play a role in the pathophysiology of tension-type headache. Investigation of CGRP in other compartments with new sensitive methods of analysis is necessary to clarify its role in tension-type headache. KEY WORDS: tension-type headache, calcitonin gene-related peptide DOMAINS: neurology Ashina: Calcitonin Gene-Related Peptide in Tension Headache TheScientificWorldJOURNAL (2002) 2, 1527-1531 1528 INTRODUCTION Chronic tension-type headache is one of the most common and important types of primary headaches In the last 10 years there has been increasing interest on the role of neuropeptides in primary headaches. Particularly, a role for calcitonin gene-related peptide (CGRP) has been implicated in the pathophysiology of neurovascular primary headaches such as migraine CGRP AND NOCICEPTION CGRP, a 37-amino acid peptide, is one of the most abundant neuropeptides in the peripheral and central nervous system CGRP IN CHRONIC TENSION-TYPE HEADACHE The role of neuropeptides in chronic tension-type headache has previously been investigated in one study The question is how to explain increased plasma CGRP in chronic tension-type headache patients with pulsating headache quality. Since CGRP levels are increased in migraineurs CONCLUDING REMARKS Studies on the role of CGRP in chronic tension-type headache indicate that plasma levels of CGRP are normal in patients and largely unrelated to headache state ACKNOWLEDGMENT

Migraine

Migraine is a common headache disorder. This Primer by Ferrari and colleagues summarizes the epidemiology, pathophysiology, diagnosis and treatment of migraine. Moreover, quality of life issues faced by patients with migraine and future research avenues are discussed.Migraine is a common, chronic, disorder that is typically characterized by recurrent disabling attacks of headache and accompanying symptoms, including aura. The aetiology is multifactorial with rare monogenic variants. Depression, epilepsy, stroke and myocardial infarction are comorbid diseases. Spreading depolarization probably causes aura and possibly also triggers trigeminal sensory activation, the underlying mechanism for the headache. Despite earlier beliefs, vasodilation is only a secondary phenomenon and vasoconstriction is not essential for antimigraine efficacy. Management includes analgesics or NSAIDs for mild attacks, and, for moderate or severe attacks, triptans or 5HT(1B/1D) receptor agonists. Because of cardiovascular safety concerns, unreliable efficacy and tolerability issues, use of ergots to abort attacks has nearly vanished in most countries. CGRP receptor antagonists (gepants) and lasmiditan, a selective 5HT1(F) receptor agonist, have emerged as effective acute treatments. Intramuscular onabotulinumtoxinA may be helpful in chronic migraine (migraine on >= 15 days per month) and monoclonal antibodies targeting CGRP or its receptor, as well as two gepants, have proven effective and well tolerated for the preventive treatment of migraine. Several neuromodulation modalities have been approved for acute and/or preventive migraine treatment. The emergence of new treatment targets and therapies illustrates the bright future for migraine management.Paroxysmal Cerebral Disorder

Guidelines of the International Headache Society for controlled trials of preventive treatment of chronic migraine in adults

Paroxysmal Cerebral Disorder

Guidelines of the International Headache Society for controlled trials of acute treatment of migraine attacks in adults: Fourth edition

Paroxysmal Cerebral Disorder

Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine: The multicentre, double-blind, randomised, sham-controlled PREMIUM trial

Introduction: Non-invasive vagus nerve stimulation (nVNS; gammaCore®) has the potential to prevent migraine days in patients with migraine on the basis of mechanistic rationale and pilot clinical data. Methods: This multicentre study included a 4-week run-in period, a 12-week double-blind period of randomised treatment with nVNS or sham, and a 24-week open-label period of nVNS. Patients were to administer two 120-second stimulations bilaterally to the neck three times daily (6–8 hours apart). Results: Of 477 enrolled patients, 332 comprised the intent-to-treat (ITT) population. Mean reductions in migraine days per month (primary outcome) were 2.26 for nVNS (n = 165; baseline, 7.9 days) and 1.80 for sham (n = 167; baseline, 8.1 days) (p = 0.15). Results were similar across other outcomes. Upon observation of suboptimal adherence rates, post hoc analysis of patients with ≥ 67% adherence per month demonstrated significant differences between nVNS (n = 138) and sham (n = 140) for outcomes including reduction in migraine days (2.27 vs. 1.53; p = 0.043); therapeutic gains were greater in patients with aura than in those without aura. Most nVNS device-related adverse events were mild and transient, with application site discomfort being the most common. Conclusions: Preventive nVNS treatment in episodic migraine was not superior to sham stimulation in the ITT population. The “sham” device inadvertently provided a level of active vagus nerve stimulation. Post hoc analysis showed significant effects of nVNS in treatment-adherent patients. Study identification and registration: PREMIUM; NCT02378844; https://clinicaltrials.gov/ct2/show/NCT02378844. © International Headache Society 2019

C. Eric Lincoln's Birthday at Alex Haley's Farm, 1990

C. Eric Lincoln stands with guests on a porch outside of Alex Haley's house in Tennessee.The Atlanta University Center Robert W. Woodruff Library acknowledges the generous support of the National Endowment for Humanities - Humanities Collections and Reference Resources Implementation Project Grant in supporting the processing and digitization of a number of its major archival collections as part of the project: Spreading the Word: Expanding Access to African American Religious Archival Collections at the Atlanta University Center Robert W. Woodruff Library.</em

Guidelines for controlled trials of preventive treatment of migraine attacks in episodic migraine in adults

Clinical trials are a key component of the evidence base for the treatment of headache disorders. In 1991, the International Headache Society Clinical Trials Standing Committee developed and published the first edition of theGuidelines for Controlled Trials of Drugs in Migraine. Advances in drugs, devices, and biologicals, as well as novel trial designs, have prompted several updates over the nearly 30 years since, including most recently theGuidelines for controlled trials of preventive treatment of chronic migraine(2018), theGuidelines for controlled trials of acute treatment of migraine attacks in adults(2019), andGuidelines for controlled trials of preventive treatment of migraine in children and adolescents(2019). The present update incorporates findings from new research and is intended to optimize the design of controlled trials of preventive pharmacological treatment of episodic migraine in adults. A guideline for clinical trials with devices will be published separately.Paroxysmal Cerebral Disorder

Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine: The multicentre, double-blind, randomised, sham-controlled PREMIUM trial

Introduction: Non-invasive vagus nerve stimulation (nVNS; gammaCore) has the potential to prevent migraine days in patients with migraine on the basis of mechanistic rationale and pilot clinical data. Methods: This multicentre study included a 4-week run-in period, a 12-week double-blind period of randomised treatment with nVNS or sham, and a 24-week open-label period of nVNS. Patients were to administer two 120-second stimulations bilaterally to the neck three times daily (6–8 hours apart). Results: Of 477 enrolled patients, 332 comprised the intent-to-treat (ITT) population. Mean reductions in migraine days per month (primary outcome) were 2.26 for nVNS (n ¼ 165; baseline, 7.9 days) and 1.80 for sham (n ¼ 167; baseline, 8.1 days) (p ¼ 0.15). Results were similar across other outcomes. Upon observation of suboptimal adherence rates, post hoc analysis of patients with 67% adherence per month demonstrated significant differences between nVNS (n ¼ 138) and sham (n ¼ 140) for outcomes including reduction in migraine days (2.27 vs. 1.53; p ¼ 0.043); therapeutic gains were greater in patients with aura than in those without aura. Most nVNS device-related adverse events were mild and transient, with application site discomfort being the most common. Conclusions: Preventive nVNS treatment in episodic migraine was not superior to sham stimulation in the ITT population. The ‘‘sham’’ device inadvertently provided a level of active vagus nerve stimulation. Post hoc analysis showed significant effects of nVNS in treatment-adherent patients