An underrepresented majority: A systematic review utilizing allodynic criteria to examine the present scarcity of discrete animal models for episodic migraine

Cephalalgia ◽  
2020 ◽  
pp. 033310242096698
Author(s):  
Aidan Levine ◽  
Todd W Vanderah ◽  
Tally M Largent-Milnes
Keyword(s):  
Animal Models ◽  
Chronic Migraine ◽  
Medication Overuse ◽  
Episodic Migraine ◽  
Non Invasive ◽  
The Past ◽  
Inflammatory Soup ◽  
Distinct Disease ◽  
Post Traumatic ◽  
Episodic Migraineurs

Background Despite increasing evidence differentiating episodic and chronic migraine, little work has determined how currently utilized animal models of migraine best represent each distinct disease state. Aim In this review, we seek to characterize accepted preclinical models of migraine-like headache by their ability to recapitulate the clinical allodynic features of either episodic or chronic migraine. Methods From a search of the Pu bMed database for “animal models of migraine”, “headache models” and “preclinical migraine”, we identified approximately 80 recent (within the past 20 years) publications that utilized one of 10 different models for migraine research. Models reviewed fit into one of the following categories: Dural KCl application, direct electrical stimulation, nitroglycerin administration, inflammatory soup injection, CGRP injection, medication overuse, monogenic animals, post-traumatic headache, specific channel activation, and hormone manipulation. Recapitulation of clinical features including cephalic and extracephalic hypersensitivity were evaluated for each and compared. Discussion Episodic migraineurs comprise over half of the migraine population, yet the vast majority of current animal models of migraine appear to best represent chronic migraine states. While some of these models can be modified to reflect episodic migraine, there remains a need for non-invasive, validated models of episodic migraine to enhance the clinical translation of migraine research.

Functional connectivity of hypothalamus in chronic migraine with medication overuse

Cephalalgia ◽  
2019 ◽  
Vol 39 (7) ◽  
pp. 892-899 ◽  
Author(s):  
Fleur Lerebours ◽  
Kader Boulanouar ◽  
Michèle Barège ◽  
Marie Denuelle ◽  
Fabrice Bonneville ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Chronic Migraine ◽  
Medication Overuse ◽  
Episodic Migraine ◽  
Anterior Hypothalamus ◽  
Spinal Trigeminal Nucleus ◽  
Trigeminal Nucleus ◽  
Chronic Group ◽  
Trigeminal Nuclei ◽  
The Right

Objective To investigate the functional connectivity of the hypothalamus in chronic migraine compared to interictal episodic migraine in order to improve our understanding of migraine chronification. Methods Using task-free fMRI and ROI-to-ROI analysis, we compared anterior hypothalamus intrinsic connectivity with the spinal trigeminal nucleus in patients with chronic migraine (n = 25) to age- and sex-matched patients with episodic migraine in the interictal phase (n = 22). We also conducted a seed-to-voxel analysis with anterior hypothalamus as a seed. Results All patients with chronic migraine had medication overuse. We found a significant connectivity (T = 2.08, p = 0.024) between anterior hypothalamus and spinal trigeminal nucleus in the chronic group, whereas these two regions were not connected in the episodic group. The strength of connectivity was not correlated with pain intensity (rho: 0.09, p = 0.655). In the seed-to-voxel analysis, three regions were more connected with the anterior hypothalamus in the chronic group: The spinal trigeminal nuclei (MNI coordinate x = 2, y = −44, z = −62), the right dorsal anterior insula (MNI coordinate x = 10, y = 10, z = 18), and the right caudate (MNI coordinate x = 12, y = 28, z = 6). However, these correlations were no longer significant after whole brain FWE correction. Conclusion An increased functional connectivity between the anterior hypothalamus and the spinal trigeminal nucleus, as previously reported in preictal episodic migraine, was demonstrated in chronic migraine with medication overuse. This finding confirms a major role of the anterior hypothalamus in migraine and suggests that chronic migraineurs are locked in the preictal phase.

scholarly journals Correlation between migraine subtipes and depression

2008 ◽  
Vol 66 (3a) ◽  
pp. 485-487 ◽  
Author(s):  
Renan Barros Domingues ◽  
Esther Angélica Coelho Costa ◽  
Ariovaldo da Silva Jr ◽  
Simone Aires Domingues ◽  
Juliana Cardoso Leal ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Chronic Migraine ◽  
Beck Depression Inventory ◽  
Medication Overuse ◽  
Episodic Migraine ◽  
The Mean ◽  
Asymptomatic Subjects

This study has evaluated depression in patients with episodic migraine (n=98), chronic migraine without medication overuse (n=23), and chronic migraine with medication overuse (n=57). The Beck Depression Inventory (BDI) was used to evaluate depressive symptoms in these three groups. The mean BDI score obtained in all patients was higher than that observed in asymptomatic subjects (episodic migraine=16.09±11.79, chronic migraine with medication overuse=18.91±12.53, chronic migraine without medication overuse=19.83±14.79). This finding corroborates previous studies suggesting a co-morbid association between migraine and depression. Depression did not seem to be crucial in the transformation of migraine as the median BDI scores did not differ significantly between patients with episodic and chronic migraine. The median BDI scores of the patients with chronic migraine with medication overuse and that patients with chronic migraine without medication overuse were similar as well. Therefore, medication overuse behavior may not be related with depression.

Prevalence of right-to-left shunts on transcranial Doppler in chronic migraine and medication-overuse headache

Cephalalgia ◽  
2013 ◽  
Vol 34 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Song Guo ◽  
Sarvnaz Shalchian ◽  
Pascale Gérard ◽  
Michael Küper ◽  
Zaza Katsarava ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Transcranial Doppler ◽  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Episodic Migraine ◽  
Severe Form ◽  
Cross Sectional ◽  
Headache Clinic ◽  
Chronic Headaches ◽  
Chronic Migraineurs

Background It was suggested that right-to-left shunt (RLS) may be highly prevalent in chronic migraine (CM) patients, indicating that patent foramen ovale (PFO) might be an aggravating and chronifying factor of migraine. Since a high proportion of chronic migraineurs also have medication-overuse headache (MOH), one may wonder if they have a more severe form of the disorder and more frequently a PFO. Objective The objective of this study is to determine the prevalence and grade of RLS in patients suffering from CM and MOH. Methods A cross-sectional multicenter study of air-contrast transcranial Doppler was conducted in 159 patients with CM ( n = 57) or MOH ( n = 102) attending a tertiary headache clinic. Results The prevalence of RLS in CM was 37% (11% large shunts) and in MOH patients 31% (13% large shunts). There was no difference between the two groups ( p = 0.49). Conclusion RLS prevalence in CM is within the upper range of those reported in episodic migraine without aura or in the general population, and not higher in MOH. PFO is thus unlikely to have a significant causal role in these chronic headaches.

Analysis of Leukocytes in Medication-Overuse Headache, Chronic Migraine, and Episodic Migraine

2011 ◽  
Vol 51 (8) ◽  
pp. 1228-1238 ◽  
Author(s):  
Cassiano M. Forcelini ◽  
Denise C. M. Dantas ◽  
Clarice Luz ◽  
Ricardo Santin ◽  
Airton T. Stein ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Medication Overuse ◽  
Medication Overuse Headache ◽  
Episodic Migraine

scholarly journals Vitamin D, Chronic Migraine, and Extracranial Pain: Is There a Link? Data From an Observational Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Valentina Rebecchi ◽  
Daniela Gallo ◽  
Lucia Princiotta Cariddi ◽  
Eliana Piantanida ◽  
Payam Tabaee Damavandi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Chronic Migraine ◽  
Medication Overuse ◽  
Primary Headache ◽  
Episodic Migraine ◽  
Tension Type Headache ◽  
Exact Test ◽  
Pain Chronification ◽  
Type Headache

Several studies focused on the role of vitamin D (vitD) in pain chronification. This study focused on vitD level and pain chronification and extension in headache disorders. Eighty patients with primary headache underwent neurological examination, laboratory exams, including serum calcifediol 25(OH)D, and headache features assessment along with three questionnaires investigating depression, anxiety, and allodynia. The 86.8% of the population had migraine (48% episodic and 52% chronic). The 44.1% of patients had extracranial pain, and 47.6% suffered from allodynia. A vitD deficit, namely a serum 25(OH)D level <20 ng/ml, was detectable in 46.1% of the patients, and it occurred more frequently (p = 0.009) in patients suffering from chronic migraine (CM)–medication overuse migraine (MOH) (62.9%) than in episodic migraine (EM, 25.7%) or tension-type headache (TTH, 11.4%). The occurrence of extracranial pain and allodynia was higher in the CM-MOH than in the EM and in the TTH groups but was not related to the co-occurrence of vitD deficiency (Fisher's exact test p = 0.11 and p = 0.32, respectively). Our findings show that 25(OH)D deficit is also related to chronic headache, probably because of vitD anti-inflammatory and tolerogenic properties, reinforcing the idea of a neuroinflammatory mechanism underpinning migraine chronification.

Field Testing Alternative Criteria for Chronic Migraine

Cephalalgia ◽  
2006 ◽  
Vol 26 (4) ◽  
pp. 477-482 ◽  
Author(s):  
ME Bigal ◽  
SJ Tepper ◽  
FD Sheftell ◽  
AM Rapoport ◽  
RB Lipton
Keyword(s):  
Chronic Migraine ◽  
Chronic Daily Headache ◽  
Medication Overuse ◽  
Field Testing ◽  
Episodic Migraine ◽  
Headache Disorders ◽  
Transformed Migraine ◽  
Daily Headache ◽  
Probable Migraine

The criteria for chronic migraine (CM), as proposed by the Second Edition of the International Classification of Headache Disorders (ICHD-2) is very restrictive, excluding most patients that evolve from episodic migraine. In this study we empirically tested three recent proposals for revised criteria for CM. We included individuals with transformed migraine (TM) with or without medication overuse, according to the criteria proposed by Silberstein and Lipton. All individuals had headache calendars for at least three consecutive months. We assessed the proportion of subjects that fulfilled ICHD-2 criteria for CM or probable chronic migraine with probable medication overuse (CM+). We also tested three proposals for making the CM criteria more inclusive. In proposal 1, CM/CM+ would require at least 15 days of migraine or probable migraine per month. Proposal 2 suggests that CM/CM+ would be classified in those with ≥15 days of headache per month, where at least 50% of these days are migraine or probable migraine. Proposal 3 suggests that CM/CM+ would be classified in those with chronic daily headache and at least 8 days of migraine or probable migraine per month. Among TM sufferers, 399 (62.5%) had TM with medication overuse, and just 10.2% were classified as CM+ 158 (37.5%) had TM without medication overuse; just nine (5.6%) met current ICHD-2 criteria for CM. Using the alternative criteria, proposal 1 included 48.7% of patients with TM without medication overuse; proposal 2 captured 88%, and proposal 3 classified 94.9% of these patients. For TM with medication overuse, the proportions for proposals 1-3 were, respectively, 37%, 81% and 91%. The differences were statistically significant, favouring proposal 3. Consistently, criteria for CM and CM+ should be revised to require at least 8 days of migraine or probable migraine per month, in individuals with 15 or more days of headache per month.

Factors associated to chronic migraine with medication overuse: A cross-sectional study

Cephalalgia ◽  
2018 ◽  
Vol 38 (14) ◽  
pp. 2045-2057 ◽  
Author(s):  
Michele Viana ◽  
Sara Bottiroli ◽  
Grazia Sances ◽  
Natascia Ghiotto ◽  
Marta Allena ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Chronic Migraine ◽  
Medication Overuse ◽  
Episodic Migraine ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Factors Associated ◽  
Preventive Medication ◽  
History Of

Background and aim Factors implicated in the evolution of episodic migraine into chronic migraine are largely elusive. Medication overuse is considered to be one of the main determinants, but other possible clinical and psychological factors can play a role. The aim of this study is to identify factors that are associated with chronic migraine with medication overuse. Method We enrolled consecutive migraine patients, subdividing them in two groups: Subjects with a long history of episodic migraine and subjects with chronic migraine and medication overuse. We then compared their clinical and psychological variables in a cross-sectional study. Results Three hundred and eighteen patients were enrolled, of which 156 were episodic migraine and 162 were chronic migraine and medication overuse patients. The mean age was 42.1 ± 10.3, 80.8% were female. The duration of migraine was 24.6 years in episodic migraine and 24.0 years in chronic migraine and medication overuse ( p = 0.57). After the multivariate analysis, the factors associated to chronic migraine and medication overuse were: Marital status (married vs. unmarried, OR 3.65, 95% CI 1.63–8.19, p = 0.002; separated/divorced/widowed vs. unmarried, OR 4.19, 95% CI 1.13–15.47, p = 0.031), physical activity (OR 0.42, 95% CI 0.19–0.91, p = 0.029), age at onset of migraine (OR 0.94, 95% CI 0.89–0.98, p = 0.016), use of at least one migraine preventive medication (OR 2.36, 95% CI 1.18–4.71, p = 0.014), history of depression (OR 2.91, 95% CI 1.25–6.73, p = 0.012), insomnia associated with the use of hypnotics (OR 5.59, 95% CI 1.65–18.93, p = 0.006), traumatic head injuries (OR 3.54, 95% CI 1.57–7.99, p = 0.002), snoring (OR 2.24, 95% CI 1.05–4.79, p = 0.036), previous and/or actual use of combined oral contraceptives (OR 3.38, 95% CI 1.10–10.3, p = 0.031) and higher scores in the Childhood Trauma questionnaire (OR 1.48, 95% CI 1.09–2.02, p = 0.012). Conclusion We considered several aspects that may be involved in the development of chronic migraine and medication overuse. A multivariate analysis identified 10 factors belonging to five different areas, to suggest that chronic migraine and medication overuse onset is likely influenced by a complex mixture of factors. This information is useful when planning strategies to prevent and manage chronic migraine and medication overuse.

Medication overuse in a subgroup analysis of phase 3 placebo-controlled studies of galcanezumab in the prevention of episodic and chronic migraine

Cephalalgia ◽  
2020 ◽  
pp. 033310242096665
Author(s):  
David W Dodick ◽  
Erin G Doty ◽  
Sheena K Aurora ◽  
Dustin D Ruff ◽  
Virginia L Stauffer ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Subgroup Analysis ◽  
Repeated Measures ◽  
Migraine Headache ◽  
Medication Overuse ◽  
Preventive Treatment ◽  
Episodic Migraine ◽  
Phase 3 ◽  
Double Blind ◽  
Acute Medication

Introduction Acute medication overuse is prevalent in patients with migraine. Methods In three phase 3, double-blind, randomized, placebo-controlled studies, patients with episodic migraine (EVOLVE-1 and EVOLVE-2) or chronic migraine (REGAIN) were randomized 2:1:1 to monthly subcutaneous injections of placebo or galcanezumab 120 or 240 mg for 3 or 6 months. This subgroup analysis evaluated mean changes in the number of monthly migraine headache days in each treatment among patients with versus without baseline acute medication overuse via mixing modelling with repeated measures. Results The percentages of patients with baseline medication overuse in placebo, galcanezumab 120-mg and 240-mg groups, respectively, were 19.4%, 17.3%, and 19.3% for EVOLVE-1/-2 (pooled; post hoc), and 63.4%, 64.3%, and 64.1% for REGAIN ( a priori). Both galcanezumab doses demonstrated significant improvement compared with placebo for overall least squares mean change in monthly migraine headache days in patients with baseline medication overuse in both the episodic and chronic migraine studies ( p ≤ 0.001). Furthermore, both galcanezumab doses reduced average monthly medication overuse rates compared to placebo ( p < 0.001) in both patient populations with medication overuse at baseline. Conclusions Galcanezumab appears to be effective for the preventive treatment of episodic and chronic migraine in patients who overuse acute medications. Trial registration: ClinicalTrials.gov Identifiers: NCT02614183, NCT02614196, and NCT02614261

Topiramate and Triptans Revert Chronic Migraine With Medication Overuse to Episodic Migraine

2006 ◽  
Vol 29 (5) ◽  
pp. 269-275 ◽  
Author(s):  
Daniele Mei ◽  
Diana Ferraro ◽  
Giovanni Zelano ◽  
Alessandro Capuano ◽  
Catello Vollono ◽  
...  
Keyword(s):  
Chronic Migraine ◽  
Medication Overuse ◽  
Episodic Migraine

Persistent post-traumatic headache attributed to mild traumatic brain injury: Deep phenotyping and treatment patterns

Cephalalgia ◽  
2020 ◽  
Vol 40 (6) ◽  
pp. 554-564 ◽  
Author(s):  
Håkan Ashina ◽  
Afrim Iljazi ◽  
Haidar Muhsen Al-Khazali ◽  
Sait Ashina ◽  
Rigmor Højland Jensen ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Chronic Migraine ◽  
Mild Traumatic Brain Injury ◽  
Structured Interview ◽  
Episodic Migraine ◽  
Treatment Patterns ◽  
Preventive Medication ◽  
Post Traumatic ◽  
Deep Phenotyping

Objective To investigate clinical characteristics and treatment patterns in persistent post-traumatic headache attributed to mild traumatic brain injury. Methods A total of 100 individuals with persistent post-traumatic headache attributed to mild traumatic brain injury were enrolled between July 2018 and June 2019. Deep phenotyping was performed using a semi-structured interview while allodynia was assessed using the 12-item Allodynia Symptom Checklist. Results In 100 subjects with persistent post-traumatic headache, the mean headache frequency was 25.4 ± 7.1 days per month. The most common headache phenotype was chronic migraine-like headache (n = 61) followed by combined episodic migraine-like and tension-type-like headache (n = 29) while nine subjects reported “pure” chronic tension-type-like headache. The most frequent trigger factors were stress, lack of sleep, and bright lights. A history of preventive medication use was reported by 63 subjects, of which 79% reported failure of at least one preventive drug, while 19% reported failure of at least four preventive drugs. Cutaneous allodynia was absent in 54% of the subjects, mild in 23%, moderate in 17%, and severe in 6%. Conclusions The headache profile of individuals with persistent post-traumatic headache most often resembled a chronic migraine-like phenotype or a combined episodic migraine-like and tension-type-like headache phenotype. Migraine-specific preventive medications were largely reported to be ineffective. Therefore, there is a pressing need for pathophysiological insights and disease-specific therapies.

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