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Sensitivity of tissues can be measured by algometry. Decreased pressure pain thresholds over the cranio-cervical area are supposed to reflect signs of sensitization of the trigemino-cervical nucleus caudalis. A systematic review was conducted to assess the current scientific literature describing pressure pain threshold (PPT) values over the cranio-cervical region in patients with migraine, tension-type headache (TTH), and cervicogenic headache (CeH). A literature search was executed in three databases. The search strategy included the following keywords: migraine, TTH, CeH, PPT and algometry. A total of 624 papers was identified of which relevant papers were subsequently assessed for methodological quality. Twenty-two selected papers were assessed by two independent reviewers and the majority of studies scored low risk of bias on the selected items. Mean PPT values of several sites measured in the cranio-cervical region in patients with migraine, chronic TTH and CeH scored lower values compared to controls. The trapezius muscle (midpoint between vertebrae C7 and acromion) was the most frequently targeted site and showed significantly lower PPT values in adults with migraine (pooled standardized mean difference kPa: 1.26 [95%CI -1.71, -0.81]) and chronic TTH (pooled standardized mean difference kPa: -2.00 [95%CI -2.93, -1.08]). Most studies found no association between PPT values and headache characteristics such as frequency, duration or intensity. Further standardization of PPT measurement in the cranio-cervical region is recommended.
Stimulation of the occipital or trigeminal nerves has been successfully used to treat chronic refractory neurovascular headaches such as migraine or cluster headache, and painful neuropathies. Convergence of trigeminal and occipital sensory afferents in the 'trigeminocervical complex' (TCC) from cutaneous, muscular, dural, and visceral sources is a key mechanism for the input-induced central sensitization that may underlie the altered nociception. Both excitatory (glutamatergic) and inhibitory (GABAergic and glycinergic) mechanisms are involved in modulating nociception in the spinal and medullary dorsal horn neurons, but the mechanisms by which nerve stimulation effects occur are unclear. This study was aimed at investigating the acute effects of electrical stimulation of the greater occipital nerve (GON) on the responses of neurons in the TCC to the mechanical stimulation of the vibrissal pad.
The aim of this study was to examine the effects of high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex (M1) on subjective pain and evoked responses induced by laser stimulation (LEPs) of the contralateral hand and supraorbital zone in a cohort of migraine patients without aura during the inter-critical phase, and to compare the effects with those of non-migraine healthy controls. Thirteen migraine patients and 12 sex- and age-matched controls were evaluated. Each rTMS session consisted of 1,800 stimuli at a frequency of 5 Hz and 90% motor threshold intensity. Sham (control) rTMS was performed at the same stimulation position. The vertex LEP amplitude was reduced at the trigeminal and hand levels in the sham-placebo condition and after rTMS to a greater extent in the migraine patients than in healthy controls, while the laser pain rating was unaffected. These results suggest that HF rTMS of motor cortex and the sham procedure can both modulate pain-related evoked responses in migraine patients.
Accumulating studies have indicated a wide range of brain alterations with respect to the structure and function of classic trigeminal neuralgia (CTN). Given the dynamic nature of pain experience, the exploration of temporal fluctuations in interregional activity covariance may enhance the understanding of pain processes in the brain. The present study aimed to characterize the temporal features of functional connectivity (FC) states as well as topological alteration in CTN.
The pathogenesis of pediatric migraine remains unclear and presents challenges in diagnosis. Recently, growing evidence has indicated that the gut microbiota can exert modulatory functions at the gut-brain axis by directly or indirectly regulating tryptophan metabolism. Consequently, we aimed to elucidate the potential association among gut microbiota, tryptophan metabolism, and pediatric migraine while also identifying diagnostic biomarkers for pediatric migraine.
To test the hypothesis that calcitonin gene-related peptide (CGRP) modulates brain activity, we investigated the effect of intravenous CGRP on brain activity in response to a visual stimulus. In addition, we examined if possible alteration in brain activity was reversed by the anti-migraine drug sumatriptan. Eighteen healthy volunteers were randomly allocated to receive CGRP infusion (1.5 μg/min for 20 min) or placebo. In vivo activity in the visual cortex was recorded before, during and after infusion and after 6 mg subcutaneous sumatriptan by functional magnetic resonance imaging (3 T). 77% of the participants reported headache after CGRP. We found no changes in brain activity after CGRP (P = 0.12) or after placebo (P = 0.41). Sumatriptan did not affect brain activity after CGRP (P = 0.71) or after placebo (P = 0.98). Systemic CGRP or sumatriptan has no direct effects on the BOLD activity in visual cortex. This suggests that in healthy volunteers both CGRP and sumatriptan may exert their actions outside of the blood-brain barrier.
Nausea is a common and disabling symptom of migraine. The origin of nausea is not well understood although functional connections between trigeminal neurons and the nucleus tractus solitarius may explain occurrence of nausea with pain. However, nausea occurs as a premonitory symptom in about a quarter of patients, suggesting that a primary brain alteration unrelated to the experience of pain may be the reason for nausea.
Serotonin is involved in several central nervous system functions including pain threshold, mood regulation and drug reward. Overuse of acute medications is commonly identified as a causative factor for medication overuse headache (MOH). Apparently, MOH shares with other kinds of drug addiction some common neurobiological pathways. The objective of this study is to assess the role of serotonin metabolism genes in the genetic liability to MOH. We performed a genetic association study using polymorphisms of five serotonin metabolism-related genes: serotonin transporter (5HTT), serotonin receptor 1A(5-HT1A), serotonin receptor 1B (5-HT1B), serotonin receptor 2A (5-HT2A) and serotonin receptor 6 (5HT6)genes. We compared 138 patients with MOH with a control sample of 117 individuals without headache and without drug overuse, and with 101 patients with migraine without aura but without drug overuse (MO). The genotypic and allelic distributions of all polymorphisms investigated didnot differ among the three groups. In conclusion, our studydoes not provide evidence that the 5HTT, 5-HT1A, 5HT1B,5HT2A and 5HT6 gene polymorphisms play a role in the genetic predisposition to MOH.
Migraine is a multifactorial disorder that is more frequent (two to four times) in women than in men. In recent years, our research group has focused on the role of neurotransmitter release and its regulation. Neurexin (NRXN2) is one of the components of the synaptic vesicle machinery, responsible for connecting intracellular fusion proteins and synaptic vesicles. Our aim was to continue exploring the role and interaction of proteins involved in the control and promotion of neurotransmission in migraine susceptibility.
As the most abundant excitatory neurotransmitter in the central nervous system, glutamate has been accepted to play a major role in the pathophysiology of migraine. The previous studies have reported the glutamate receptor ionotropic GRIA1 and GRIA3 genes variants associated with migraine. The project aims to investigate the polymorphisms in both genes for their association with migraine in the Chinese Han population.
Resting-state functional magnetic resonance imaging (RS-fMRI) has demonstrated disrupted default mode network (DMN) connectivity in a number of pain conditions, including migraine. However, the significance of altered resting-state brain functional connectivity in migraine is still unknown. The present study is aimed to explore DMN functional connectivity in patients with migraine without aura (MwoA) and investigate its clinical significance.
Proton magnetic resonance spectroscopy ((1)H-MRS) has been used in a number of studies to assess noninvasively the temporal changes of lactate (Lac) in the activated human brain. Migraine neurobiology involves lack of cortical habituation to repetitive stimuli and a mitochondrial component has been put forward. Our group has recently demonstrated a reduction in the high-energy phosphates adenosine triphosphate (ATP) and phosphocreatine (PCr) in the occipital lobe of migraine without aura (MwoA) patients, at least in a subgroup, in a phosphorus MRS ((31)P-MRS) study. In previous studies, basal Lac levels or photic stimulation (PS)-induced Lac levels were found to be increased in patients with migraine with aura (MwA) and migraine patients with visual symptoms and paraesthesia, paresia and/or dysphasia, respectively. The aim of this study was to perform functional (1)H-MRS at 3 T in 20 MwoA patients and 20 control subjects. Repetitive visual stimulation was applied using MR-compatible goggles with 8 Hz checkerboard stimulation during 12 min. We did not observe any significant differences in signal integrals, ratios and absolute metabolite concentrations, including Lac, between MwoA patients and controls before PS. Lac also did not increase significantly during and following PS, both for MwoA patients and controls. Subtle Lac changes, smaller than the sensitivity threshold (i.e. estimated at 0.1-0.2 μmol/g at 3 T), cannot be detected by MRS. Our study does, however, argue against a significant switch to non-aerobic glucose metabolism during long-lasting PS of the visual cortex in MwoA patients.
Previous studies in primary headache disorders showed microstructural alterations in the white matter as measured by diffusion imaging. However these investigations are not in full agreement and some of those, especially in cluster headache, restricted the analysis to only a limited number of diffusion parameters. Therefore, in the current study we examined white matter microstructure in cluster headache patients.
Major depressive disorder is a common comorbidity in migraineurs. Depression may affect the progression and prognosis of migraine. Few studies have examined the brain function in migraineurs that may cause this comorbidity. Here, we aimed to explore depression-related abnormalities in the intrinsic brain activity of interictal migraineurs with comorbid depression using resting-state functional magnetic resonance imaging.
Disrupted sleep is associated with a reciprocal influence on headaches and is one of the contributing factors in the process of chronicity. The goal of the present study was to investigate the influence of sleep on headaches using animal rapid eye movement (REM) sleep deprivation and supradural capsaicin infusion models.
Several fMRI studies in migraine assessed resting state functional connectivity in different networks suggesting that this neurological condition was associated with brain functional alteration. The aim of present study was to explore the association between cognitive functions and cerebral functional connectivity, in default mode network, in migraine patients without and with aura, during interictal episodic attack.
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