Dataset Information

Upregulation of inflammatory gene transcripts in periosteum of chronic migraineurs: Implications for extracranial origin of headache.

ABSTRACT: Chronic migraine (CM) is often associated with chronic tenderness of pericranial muscles. A distinct increase in muscle tenderness prior to onset of occipital headache that eventually progresses into a full-blown migraine attack is common. This experience raises the possibility that some CM attacks originate outside the cranium. The objective of this study was to determine whether there are extracranial pathophysiologies in these headaches.We biopsied and measured the expression of gene transcripts (mRNA) encoding proteins that play roles in immune and inflammatory responses in affected (ie, where the head hurts) calvarial periosteum of (1) patients whose CMs are associated with muscle tenderness and (2) patients with no history of headache.Expression of proinflammatory genes (eg, CCL8, TLR2) in the calvarial periosteum significantly increased in CM patients attesting to muscle tenderness, whereas expression of genes that suppress inflammation and immune cell differentiation (eg, IL10RA, CSF1R) decreased.Because the upregulated genes were linked to activation of white blood cells, production of cytokines, and inhibition of NF-?B, and the downregulated genes were linked to prevention of macrophage activation and cell lysis, we suggest that the molecular environment surrounding periosteal pain fibers is inflamed and in turn activates trigeminovascular nociceptors that reach the affected periosteum through suture branches of intracranial meningeal nociceptors and/or somatic branches of the occipital nerve. This study provides the first set of evidence for localized extracranial pathophysiology in CM. Ann Neurol 2016;79:1000-1013.

SUBMITTER: Perry CJ

PROVIDER: S-EPMC4884147 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Upregulation of inflammatory gene transcripts in periosteum of chronic migraineurs: Implications for extracranial origin of headache.

Perry Carlton J CJ Blake Pamela P Buettner Catherine C Papavassiliou Efstathios E Schain Aaron J AJ Bhasin Manoj K MK Burstein Rami R

Annals of neurology 20160505 6

<h4>Objective</h4>Chronic migraine (CM) is often associated with chronic tenderness of pericranial muscles. A distinct increase in muscle tenderness prior to onset of occipital headache that eventually progresses into a full-blown migraine attack is common. This experience raises the possibility that some CM attacks originate outside the cranium. The objective of this study was to determine whether there are extracranial pathophysiologies in these headaches.<h4>Methods</h4>We biopsied and measur ...[more]

PMID: 27091721

Similar Datasets

Project description:BackgroundVarious stimuli can trigger migraines in susceptible individuals. We examined migraine trigger factors by using a smartphone headache diary application.MethodEpisodic migraineurs who agreed to participate in our study downloaded smartphone headache diary application, which was designed to capture the details regarding headache trigger factors and characteristics for 3 months. The participants were asked to access the smartphone headache diary application daily and to confirm the presence of a headache and input the types of trigger factors.ResultsSixty-two participants kept diary entries until the end of the study. The diary data for 4,579 days were analyzed. In this data set, 1,099 headache days (336 migraines, 763 non-migraine headaches) were recorded; of these, 772 headache events had with trigger factors, and 327 events did not have trigger factors. The common trigger factors that were present on headache days included stress, fatigue, sleep deprivation, hormonal changes, and weather changes. The likelihood of a headache trigger was 57.7% for stress, 55.1% for sleep deprivation, 48.5% for fatigue, and 46.5% for any trigger. The headaches with trigger factors were associated with greater pain intensity (p<0.001), headache-related disability (p<0.001), abortive medication use (p = 0.02), and the proportion of migraine (p < 0.001), relative to those without trigger factors. Traveling (odd ratios [OR]: 6.4), hormonal changes (OR: 3.5), noise (OR: 2.8), alcohol (OR: 2.5), overeating (OR: 2.4), and stress (OR:1.8) were significantly associated with migraines compared to non-migraine headaches. The headaches that were associated with hormonal changes or noise were more often migraines, regardless of the preventive medication. The headaches due to stress, overeating, alcohol, and traveling were more often migraines without preventive medication, but it was not evident with preventive medication.ConclusionSmartphone headache diary application is an effective tool to assess migraine trigger factors. The headaches with trigger factors had greater severity or migraine features. The type of triggers and the presence of preventive medication influenced the headache characteristics; hence, an investigation of trigger factors would be helpful in understanding migraine occurrences.

Project description:BackgroundPeople with cluster headache (CH) are frequently burdened by misdiagnosis or diagnostic delay. The peculiar somatic and behavioral changes characterizing patients with CH are not useful to improve diagnostic accuracy. In our clinical experience, we noticed a typical voice quality with low and croaking tone in patients with CH. In this cross-sectional study, we evaluated, by digital voice analysis, whether it is possible to identify typical voice quality characterizing patients with CH compared with healthy controls (HCs). Furthermore, to investigate whether putative differences in voice characteristics could be underpinned by constitutional aspects or pathological processes of vocal cords, subjects underwent a videolaryngostroboscopy. Smoking habits and alcohol consumption were specifically investigated.MethodsAfter conducting digital recording of the voices from both patients with CH and HCs in a soundproof insulated cabin in the laboratory of the Audiology Department, a set of voice parameters was analyzed. We included the measures of fundamental frequency, calculations of jitter and shimmer, and noise-to-harmonics ratios as well as quantities related to the spectral tilt (i.e., H1-H2, H1-A1, H1-A2, and H1-A3) in 20 patients with CH and in 13 HCs. A videolaryngostroboscopy was performed in all subjects.ResultsPatients with CH, explored during the cluster bout period, showed significantly lower second harmonic (H1-H2) values compared with HCs (-6.9 ± 7.6 vs. 2.1 ± 6.7, p = 0.002), usually characterizing the so-called creaky voice. By using a laryngoscopy investigation, a significantly higher prevalence of mild to moderate vocal cord edema and laryngopharyngeal reflux signs were found in patients with CH (100% of patients with CH vs. 15% of HC, p < 0.001).ConclusionCreaky phonation is a "physiological mode of laryngeal operation" usually underpinned by shortened and thickened vocal folds. Creaky voice phonation can be due to a vocal fold's reduced capability to become slack or flaccid secondary to vocal cord edema underpinned by laryngopharyngeal reflux affecting the phonatory mechanisms in patients with CH. The laryngopharyngeal reflux may represent a dysautonomic sign related to the increased parasympathetic tone during in-bout period, reinforcing the hypothesis of an extracranial autonomic dysfunction as part of CH clinical picture.

Project description:Background:Cluster headache (CH) is considered to be a catastrophic disease presenting the most severe human pain condition. Available pharmacological treatments are hampered by unwanted side effects, and there is an urgent need for non-pharmacological treatment alternatives. We present a novel therapeutic approach for chronic CH, having evolved from an episodic CH, using a non-invasive percutaneous bioelectric current stimulation (PBCS), which generates static electric fields in the range of the naturally occurring electric potentials. Patients and Methods:This study employed a retrospective data analysis of 20 cases of chronic cluster headache (CCH) patients, four of those having had cluster-related surgery (SPG, ONS). All patients were treated with PBCS between 2014 and 2018. Data of these patients were analyzed with respect to frequency of CH attacks and triptan application and followed up for one (20 cases) or two (12 cases) years. Results:Four weeks after the first PBCS treatment, cluster headache attacks were reduced from 2.8 to 1.7 per day and triptan application decreased from 2.5 to 1.5 times/day. Six non-responders, 4 of which had pre-CH surgery, did not show any reaction to PBCS, while 14 responders improved within 4 weeks from 2.2 to 0.7 attacks/day and 2.0 to 0.4 triptan applications/day. A 50% or greater reduction of attack frequency was observed in 10 patients after 4 weeks and in 11 patients after 12 weeks. One year after the first treatment, 13/20 patients experienced a reduction of attack frequency of 50% or more, while remarkably 10 patients were completely free of attack. After 2 years, 8 of 12 patients experienced a reduction of attack frequency of 50% or more and 7 of those were completely symptom-free. No serious adverse effects were observed. Conclusion:PBCS is a promising transformative treatment approach for CCH patients. Drug consumption was reduced significantly, and the CCH may revert back to an episodic cluster headache with increasingly long times of remission. Responders can be clearly differentiated from non-responders. The data support the need for randomized controlled trials.

Project description:Cluster headache (CH) is a debilitating headache disorder with severe consequences for patient quality of life. On-demand neuromodulation targeting the sphenopalatine ganglion (SPG) is effective in treating the acute pain and a subgroup of patients experience a decreased frequency of CH attacks.We monitored self-reported attack frequency, headache disability, and medication intake in 33 patients with medically refractory, chronic CH (CCH) in an open label follow-up study of the original Pathway CH-1 study. Patients were followed for at least 24 months (average 750?±?34 days, range 699-847) after insertion of an SPG microstimulator. Remission periods (attack-free periods exceeding one month, per the ICHD 3 (beta) definition) occurring during the 24-month study period were characterized. Attack frequency, acute effectiveness, medication usage, and questionnaire data were collected at regular clinic visits. The time point "after remission" was defined as the first visit after the end of the remission period.Thirty percent (10/33) of enrolled patients experienced at least one period of complete attack remission. All remission periods followed the start of SPG stimulation, with the first period beginning 134?±?86 (range 21-272) days after initiation of stimulation. On average, each patient's longest remission period lasted 149?±?97 (range 62-322) days. The ability to treat acute attacks before and after remission was similar (37 %?±?25 % before, 49 %?±?32 % after; p?=?0.2188). Post-remission headache disability (HIT-6) was significantly improved versus baseline (67.7?±?6.0 before, 55.2?±?11.4 after; p?=?0.0118). Six of the 10 remission patients experienced clinical improvements in their preventive medication use. At 24 months post insertion headache disability improvements remained and patient satisfaction measures were positive in 100 % (10/10).In this population of 33 refractory CCH patients, in addition to providing the ability to treat acute attacks, neuromodulation of the SPG induced periods of remission from cluster attacks in a subset of these. Some patients experiencing remission were also able to reduce or stop their preventive medication and remissions were accompanied by an improvement in headache disability.

Dataset Information

Upregulation of inflammatory gene transcripts in periosteum of chronic migraineurs: Implications for extracranial origin of headache.

Publications

Upregulation of inflammatory gene transcripts in periosteum of chronic migraineurs: Implications for extracranial origin of headache.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets