Cutaneous allodynia is more frequent in chronic migraine, and its presence and severity seems to be more associated with the duration of the disease

Benatto, Mariana Tedeschi; Carvalho, Gabriela Ferreira; Dach, Fabíola; Bigal, Marcelo E.; Chaves, Thaís Cristina; Bevilaqua-Grossi, Débora

doi:10.1590/0004-282x20170015

Cited by 48 publications

(28 citation statements)

References 22 publications

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“…Migraine attacks can be associated with symptoms of cutaneous allodynia 20 , 21 , which occur more frequently in chronic migraineurs 22 . We exploited this feature to show that different generations of STA rats present with consistently lower periorbital thresholds to mechanical stimulation when compared with SD rats obtained from either external vendors or when bred in house.…”

Section: Discussionmentioning

confidence: 99%

A unique inbred rat strain with sustained cephalic hypersensitivity as a model of chronic migraine-like pain

Munro

Petersen

Jansen‐Olesen

et al. 2018

Sci Rep

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Animal models of migraine-like pain enabling ongoing study of behaviour typically involve the systemic administration of chemical vasodilators or dural administration of inflammatory algogens. However, neither method mediates prolonged effects on behavior indicative of enduring pathophysiological changes occurring within dural or trigeminal pain circuits. We generated successive generations of a unique inbred rat strain, spontaneous trigeminal allodynia (STA) rats, previously reported to exhibit an episodic migraine-like behavioural phenotype. We show that both male and female STA rats display robust and sustained reductions in periorbital thresholds to cutaneous mechanical stimulation. Otherwise, the general behavior (e.g. locomotor, grooming) of these rats appeared normal. In female STA rats, the mechanical hypersensitivity was confined to the cephalic region, manifested after puberty through adolescence, and was sustained into adulthood recapitulating the clinical manifestation of migraine. We exploited this hitherto unidentified chronic phenotype to show that the migraine-specific drugs sumatriptan (5-HT 1B/1D receptor agonist) and olcegepant (CGRP receptor antagonist) could completely reverse cephalic hypersensitivity using a within subject cross-over paradigm. Our findings indicate that STA rats actually possess a phenotype indicative of migraine chronicity which is exquisitely sensitive to migraine therapeutics. This unique strain could prove to be an invaluable resource in preclinical migraine drug discovery.Animal models of migraine-like pain enabling evaluation of disease-relevant behaviours, typically in mice or rats, are frequently induced by chemical provocation using systemic administration of vasodilating agents such as nitric oxide (NO) donors or dural application of inflammatory mediators 1-6 . These models have variously proven to be of some value in the preclinical setting but have their limitations 7 . Crucially, even with repeated dosing, the systemic administration of NO donors (e.g. glyceryl trinitrate; GTN or isosorbide dinitrate) in rodents has never been reported to produce sustainable cephalic or extracephalic hypersensitivity lasting longer than 1-2 weeks 2,8-10 , thereby limiting their utility in long term behavioural studies.The use of genetic models of migraine-like pain in animals might be expected to partially mitigate such issues. Familial Hemiplegic Migraine is a rare monogenic migraine subtype associated with aura, characterized by weakness on one side of the body during the aura phase 11 . To date, the involvement of three genes has been confirmed in this migraine subtype of which the humanized knock in CACNA1A-related R192Q mouse is probably the best studied 12 . These mice display increased unilateral head grooming and are photosensitive in accordance with a migraine-like phenotype. An advantage of using such models is that the animals possess a pre-defined phenotype, circumventing the need for complicated dosing protocols using NO donors or surgical procedures (e.g. dural ...

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Section: Discussionmentioning

confidence: 99%

A unique inbred rat strain with sustained cephalic hypersensitivity as a model of chronic migraine-like pain

Munro

Petersen

Jansen‐Olesen

et al. 2018

Sci Rep

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“…In addition to excessive symptomatic medication use, thermal pain threshold (allodynia) is also a risk factor for CM (Benatto et al, 2017), which makes the relationship between opioid use and CM complex, since opioids are potent inducers of hyperalgesia/allodynia (De Felice and Porreca., 2009). Accordingly, opioid use, endogenous opioid release, and μ-opioid receptor (μOR) concentrations are critical elements for the understanding of general pathophysiology and worsening of pain in CM.…”

Section: Introductionmentioning

confidence: 99%

Impact of chronic migraine attacks and their severity on the endogenous μ-opioid neurotransmission in the limbic system

Jassar

Nascimento

Kaciroti

et al. 2019

NeuroImage: Clinical

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Objective To evaluate, in vivo , the impact of ongoing chronic migraine (CM) attacks on the endogenous μ-opioid neurotransmission. Background CM is associated with cognitive-emotional dysfunction. CM is commonly associated with frequent acute medication use, including opioids. Methods We scanned 15 migraine patients during the spontaneous headache attack (ictal phase): 7 individuals with CM and 8 with episodic migraine (EM), as well as 7 healthy controls (HC), using positron emission tomography (PET) with the selective μ-opioid receptor (μOR) radiotracer [ 11 C]carfentanil. Migraineurs were scanned in two paradigms, one with thermal pain threshold challenge applied to the site of the headache, and one without thermal challenge. Multivariable analysis was performed between the μ-opioid receptor availability and the clinical data. Results μOR availability, measured with [ 11 C]carfentanil nondisplaceable binding potential (BP ND ), in the left thalamus (P-value = 0.005) and left caudate (P-value = 0.003) were decreased in CM patients with thermal pain threshold during the ictal phase relative to HC. Lower μOR BP ND in the right parahippocampal region (P-value = 0.001) and right amygdala (P-value = 0.002) were seen in CM relative to EM patients. Lower μOR BP ND values indicate either a decrease in μOR concentration or an increase in endogenous μ-opioid release in CM patients. In the right amygdala, 71% of the overall variance in μOR BP ND levels was explained by the type of migraine (CM vs. EM: partial-R 2 = 0.47, P-value<0.001, Cohen's effect size d = 2.6SD), the severity of the attack (pain area and intensity number summation [P.A.I.N.S.]: partial-R 2 = 0.16, P-value = 0.031), and the thermal pain threshold (allodynia: partial-R 2 = 0.08). Conclusions Increased endogenous μ-opioid receptor-mediated neurotransmission is seen in the limbic system of CM patients, especially in right amygdala, which is highly modulated by the attack frequency, pain severity, and sensitivity. This study demonstrates for the first time the negative impact of chronification and exacerbation of headache attacks on the endogenous μ-opioid mechanisms of migraine patients. ClinicalTrials.gov identifier: NCT03004313

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“…In reference to allodynia, which has been considered a pathophysiological correlate of clinical progression, we observed a statistically significant and greater reduction in those patients with a decrease in headache frequency of ≥50%. We also analyzed other migraine features, observing higher proportions of aura, both visual and sensory, after 10 years.…”

Section: Discussionmentioning

confidence: 68%

How Does Migraine Change After 10 Years? A Clinical Cohort Follow‐Up Analysis

et al. 2020

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Objective.-To describe the 10-year evolution of a cohort of migraine patients, focusing on prognostic factors of improvement.Background.-Migraine is one of the most prevalent and disabling diseases and migraineurs often want to know about the evolutionary timeline of their condition. Yet, data from longitudinal studies with a long-term follow-up is scarce.Methods.-This is a 10-year longitudinal study. In 2008, we recruited 1109 consecutive migraine patients who answered an initial survey. In 2018, we did a follow-up. We compared initial and final (after 10 years) data. A reduction ≥50% in Headache days/month was considered as improvement. A comparative study was carried out to identify predictors of improvement or no improvement.Results.-After 10 years, 380 patients completed the survey (34.3% of the initial cohort), 77.1% (293/380) were women; mean age 41.0 ± 10.6 years and 73.7% (280/380) had an initial diagnosis of episodic migraine (EM). After 10 years, 48.2% (183/380) of patients did not have a medical follow-up of their migraine; 47.4% (180/380) decreased ≥50% in frequency, which increased the proportion of EM (73.7% vs 87.4%) (P < .001) as compared to the initial results. Factors independently associated with improvement were: a baseline frequency >10 days/month (OR[ 95%]: 3.04 [1.89, 4.89]; P < .001), nonsmoking (2.13 [1.23, 3.67]; P = .006) and a medical follow-up for migraine (2.45 [1.54, 3.90]; P < .001). Additionally, after 10 years, we observed a reduction in the use of preventive treatment (48.7% vs 23.5%) and an increase in monotherapy (42.2% vs 72.7%) (P < .001).Conclusion.-After 10 years, in almost half of the patients who answered the survey, migraine improved. Other than the natural pathophysiology of migraine, having a medical follow-up and healthy habits such as nonsmoking were independent factors associated with improvement.

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Cutaneous allodynia is more frequent in chronic migraine, and its presence and severity seems to be more associated with the duration of the disease

Cited by 48 publications

References 22 publications

A unique inbred rat strain with sustained cephalic hypersensitivity as a model of chronic migraine-like pain

A unique inbred rat strain with sustained cephalic hypersensitivity as a model of chronic migraine-like pain

Impact of chronic migraine attacks and their severity on the endogenous μ-opioid neurotransmission in the limbic system

How Does Migraine Change After 10 Years? A Clinical Cohort Follow‐Up Analysis

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