Ena-DATASET-LUMCNL-04-10-2016-09:01:04:938-688 - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001002726 | EGA |
REPOSITORIES: EGA
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Project description:Cluster headache is a relatively rare headache disorder, typically characterized by multiple daily, short-lasting attacks of excruciating, unilateral (peri-)orbital or temporal pain associated with autonomic symptoms and restlessness. To better understand the pathophysiology of cluster headache, we used RNA sequencing to identify differentially expressed genes and pathways in whole blood of patients with episodic (n = 19) or chronic (n = 20) cluster headache in comparison with headache-free controls (n = 20). Blood samples were subjected to globin reduction before sequencing.
| EGAS00001001918 | EGA
Project description:Background - Cluster headache (CH) is a primary neurovascular headache disorder characterized by attacks of excruciating pain accompanied by ipsilateral autonomic symptoms. CH pathophysiology is presumed to involve an activation of hypothalamic and trigeminovascular systems, but inflammation and immunological mechanisms have also been hypothesized to be of importance. Objective - A pilot study to identify differentially expressed genes during different clinical phases of CH, assuming that changes of pathophysiological importance would also be seen in peripheral venous blood. Methods - Blood samples were drawn at 3 consecutive occasions from 3 episodic CH patients: during attacks,between attacks and in remission, and at 1 occasion from 3 matchedcontrols. Global gene expression was analyzed with microarray tehnology using the Affymetrix Human Genome U133 2.0 Plus GeneChip Set, covering more than 54,000 gene transcripts, corresponding to almost 22,000 genes.
2011-04-27 | E-MTAB-631 | biostudies-arrayexpress
Project description:The sensitization of trigeminal ganglion neurons contributes to primary headache disorders such as migraine, but the specific neuronal and non-neuronal trigeminal subtypes involved remain unclear. We thus developed a cell atlas in which human and mouse trigeminal ganglia are transcriptionally and epigenomically profiled at single-cell resolution. These data describe evolutionarily conserved and human-specific gene expression patterns within each trigeminal ganglion cell type, as well as the transcription factors and gene regulatory elements that contribute to cell-type-specific gene expression. We then leverage these data to identify trigeminal ganglion cell types that are implicated both by human genetic variation associated with migraine and two mouse models of headache. This trigeminal ganglion cell atlas improves our understanding of the cell types, genes, and epigenomic features involved in headache pathophysiology and establishes a rich resource of cell-type-specific molecular features to guide the development of more selective treatments for headache and facial pain.
2022-02-26 | GSE197289 | GEO
Project description:Acute intermittent porphyria (AIP) is an autosomal dominant inborn error of heme biosynthesis due to a pathogenic mutation in the Hmbs gene, resulting in half-normal activity of hydroxymethylbilane synthase. Factors that induce hepatic heme biosynthesis induce episodic attacks in heterozygous patients. The clinical presentation of acute attacks involves the signature neurovisceral pain and may include psychiatric symptoms. Here we used a knock-in mouse line that is biallelic for the Hmbs c.500G>A (p.R167Q) mutation with ~5% of normal hydroxymethylbilane synthase activity to unravel the consequences of severe HMBS deficiency on affective behavior and brain physiology. Hmbs knock-in mice (KI mice) model the rare homozygous dominant form of AIP and were used as tool to elucidate the hitherto unknown pathophysiology of the behavioral manifestations of the disease and its neural underpinnings. Extensive behavioral analyses revealed a selective depression-like phenotype in Hmbs KI mice; transcriptomic and immunohistochemical analyses demonstrated aberrant myelination. The uncovered compromised mitochondrial function in the hippocampus of knock-in mice and its ensuing neurogenic and neuroplastic deficits lead us to propose a mechanistic role for disrupted mitochondrial energy production in the pathogenesis of the behavioral consequences of severe HMBS deficiency and its neuropathological sequelae in the brain.
2020-03-03 | GSE146212 | GEO
Project description:Harvester ants (genus Pogonomyrmex) are notable for their stings which cause intense, long-lasting pain and other neurotoxic symptoms in vertebrates. Here we show that harvester ant venoms are relatively simple and composed largely of peptide toxins. One class of peptides is primarily responsible for the long-lasting local pain of envenomation. These hydrophobic, cysteine-free peptides activate mammalian sensory neurons via potent modulation of voltage-gated sodium (NaV) channels, reducing voltage threshold for activation and inhibiting channel inactivation. These toxins appear to have evolved specifically as deterrents against vertebrates.
2024-06-16 | PXD043773 | Pride
Project description:Nociception is protective and prevents tissue damage but can also facilitate chronic pain. If a general principle governs these two types of pain is unknown. Here, we show that both basal mechanical and neuropathic pain are controlled by microRNA-183 cluster in mice. This single cluster controls more than 80% of neuropathic pain-regulated genes and scales basal mechanical sensitivity and mechanical allodynia by regulating auxiliary voltage-gated calcium channel subunits a2d. Basal sensitivity is controlled in nociceptors and allodynia involves TrkB+ light-touch mechanoreceptors. These light-touch sensitive neurons that normally do not elicit pain produce pain during neuropathy that is reversed by gabapentin. Thus, a single miRNA cluster continuously scales acute noxious mechanical sensitivity in nociceptive neurons and suppresses neuropathic pain transduction in a specific, light-touch sensitive neuronal type recruited during mechanical allodynia.
2017-05-25 | GSE99265 | GEO
Project description:Gout is a prevalent and painful inflammatory arthritis, and its global burden continues to rise. Intense pain induced by gout attacks is a major complication of gout. Treatment and long-term management for gout patients remain challenging. Despite the discovery of many key immune response and inflammatory genes and pathways in gout, the molecular mechanisms of gout inflammation are still not entirely elucidated. Particularly, systematic studies of gout inflammation and pain are lacking. Using a monosodium urate (MSU) crystals-induced gout model, we performed genome-wide transcriptome analysis for the ankle joint, dorsal root ganglion (DRG), and spinal cord of gout mice. Our results revealed transcriptional changes in both the joint and the nervous system. Furthermore, through integrated analysis with public datasets of mouse inflammatory pain and neuropathic pain models, human GWAS, osteoarthritis (OA), and rheumatoid arthritis (RA), we identified common and unique features associated with acute gout inflammation and severe pain.
2022-06-24 | GSE190138 | GEO
Project description:<p>Individuals with episodic ataxia experience recurrent attacks of dizziness and incoordination; between attacks patients are typically normal. The majority of cases are likely caused by an inherited genetic mutation. However, in some patients we are unable to identify the mutation. So far, 2 genes have been identified which cause different types of episodic ataxia. Ultimately, when the actual mutation is identified the protein product of the gene can be studied and specific medications can be designed. During this study, we will clinically evaluate patients with EA and follow them over time to help us better characterize the disease. We will also obtain blood samples to test for the known genetic mutations. In the future, we plan to coordinate trials of medications for the treatment of these disorders.</p>
| phs000521 | dbGaP
Project description:Tail amputation by tail docking or as an extreme consequence of tail biting in commercial pig production has serious implications for animal welfare. Tail amputation causes peripheral nerve injury that might be associated with chronic lasting pain. The aim of this study was to investigate the short- and long-term effects of tail amputation in pigs on caudal DRG gene expression at different stages of development, particularly in relation to genes associated with nociception and pain. Microarray analysis was used to analyse whole DRG transcriptomes from tail amputated and sham-treated pigs 1, 8 and 16 weeks following tail treatment at either 3 or 63 days of age (8 pigs/treatment/age/time after treatment; n=96). Tail amputation induced marked changes in gene expression (up and down) compared to sham-treated intact controls for all treatment ages and time points after tail treatment. Sustained changes in gene expression in tail amputated pigs were still evident approximately 4 months after tail injury. Gene correlation network analysis revealed two gene coexpression clusters associated with amputation. Gene ontology (GO) enrichment analysis found the genes in Cluster A (124 genes) and Cluster B (61 genes) to be associated with both ‘inflammatory pain’ and ‘neuropathic pain ’. Key families of ion channels and receptors were significantly down-regulated compared to shams in Cluster A, in particular voltage-gated potassium channels and GABA receptors which are both linked to increased peripheral nerve excitability after axotomy. Up-regulated functional gene families in Cluster B were linked to transcription regulation, inflammation, tissue remodelling and regulatory neuropeptide activity. DRG gene expression profiles appear to reflect sustained tissue inflammation and repair (ca. 4 months) and pain signal modulation consistent with adaptive, compensatory responses linked to injury induced increases in peripheral somatosensory neuronal excitability in the tail stump. Tail amputation causes acute and sustained changes in peripheral somatosensory nerve function involving key mediators of inflammatory and neuropathic pain which have implications for long-term tail stump pain. The findings of this study may have ramifications for the effects of tail amputation in other species. We used microarray to investigate the effects of tail amputation on gene expression in the dorsal root ganglia of caudal nerves in pigs at 2 treatment ages and 3 time points after tail treatment
2019-01-01 | GSE119519 | GEO
Project description:Nociceptors are neurons responsible for the detection of pain producing stimuli. Persistent changes in their activity, termed plasticity, benefit survival through injury avoidance and are regulated on a translational basis. Yet, the mRNAs whose translation facilitates plasticity are unknown. Here, we apply ribosome profiling to dorsal root ganglion and identify a small number of transcripts that are selectively translated in response to plasticity mediators. Among them are Arc and Fos, genes implicated in episodic learning in the brain. We demonstrate that the ribosomal S6 kinase 1 is responsible for their production in nociceptors. Blocking S6 driven translation also reduces pain associated behavioral responses in vivo. In addition to translation of coding regions of mRNA, we detect pervasive ribosome occupancy in 5’ untranslated regions. We find that peptides encoded by open reading frames in the 5’ untranslated regions of Calca and Egr2 increase neuronal excitability in vitro and are sufficient to induce pain-like behaviors in vivo. Together, our findings uncover new targets of translational control that drive changes in plasticity and suggest new mechanisms for targeted pain therapeutics that disrupt pain signaling.
2020-02-01 | GSE117043 | GEO