RNA sequencing profiling of mRNAs, lncRNAs and circRNAs in Trigeminal Ganglion following Temporomandibular Joint inflammation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE207126 | GEO | 2022/07/23
REPOSITORIES: GEO
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Project description:Purpose: In this study, we aimed to analyze lncRNA expression in the whole transcriptome of trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) in a chronic inflammatory TMJ pain mouse model. Chronic inflammatory TMJ pain was induced by intra-TMJ injection of complete Freund's adjuvant (CFA). The lncRNA expression patterns in the whole transcriptome of TG and Sp5C were profiled with RNA sequencing.
2022-06-01 | GSE188922 | GEO
Project description:Temporomandibular joint disorder (TMJD) is known for its mastication-associated pain. TMJD is medically relevant because of its prevalence, severity, chronicity, the therapy-refractoriness of its pain, and its largely elusive pathogenesis. Against this background, we sought to investigate the pathogenetic contributions of the calcium-permeable TRPV4 ion channel, robustly expressed in the trigeminal ganglion sensory neurons, to TMJ inflammation and pain behavior. We demonstrate here that TRPV4 is critical for TMJ-inflammation-evoked pain behavior in mice and that trigeminal ganglion pronociceptive changes are TRPV4-dependent. As a quantitative metric, bite force was recorded as evidence of masticatory sensitization, in keeping with human translational studies. In Trpv4(-/-) mice with TMJ inflammation, attenuation of bite force was significantly less than in wildtype (WT) mice. Similar effects were seen with systemic application of a specific TRPV4 inhibitor. TMJ inflammation and mandibular bony changes were apparent after injections of complete Freund adjuvant but were remarkably independent of the Trpv4 genotype. It was intriguing that, as a result of TMJ inflammation, WT mice exhibited significant upregulation of TRPV4 and phosphorylated extracellular-signal-regulated kinase (ERK) in TMJ-innervating trigeminal sensory neurons, which were absent in Trpv4(-/-) mice. Mice with genetically-impaired MEK/ERK phosphorylation in neurons showed resistance to reduction of bite force similar to that of Trpv4(-/-) mice. Thus, TRPV4 is necessary for masticatory sensitization in TMJ inflammation and probably functions upstream of MEK/ERK phosphorylation in trigeminal ganglion sensory neurons in vivo. TRPV4 therefore represents a novel pronociceptive target in TMJ inflammation and should be considered a target of interest in human TMJD.
| S-EPMC3722361 | biostudies-literature
Project description:Background:Women with temporomandibular disorders (TMDs) experience some amelioration of pain during pregnancy. Progesterone increases dramatically and steadily during pregnancy. Sodium channel 1.7 (Nav1.7) plays a prominent role in pain perceptions, as evidenced by deletion of Nav1.7 alone leading to a complete loss of pain. In a previous study, we showed that Nav1.7 in trigeminal ganglion (TG) is involved in allodynia of inflamed temporomandibular joint (TMJ). Whether progesterone modulates allodynia of inflamed TMJ through Nav1.7 in TG remains to be investigated. Methods:The effects of progesterone on sodium currents of freshly isolated TG neurons were examined using whole-cell recording. Female rats were ovariectomized and treated with increasing doses of progesterone for 10 days. Complete Freund's adjuvant was administered intra-articularly to induce TMJ inflammation. TMJ nociceptive responses were evaluated by head withdrawal thresholds. Real-time PCR and Western blotting were used to examine Nav1.7 mRNA and protein expression in TG. Immunohistofluorescence was used to examine the colocalization of progesterone receptors (PR?/?) and Nav1.7 in TG. Results:Whole-cell recording showed that progesterone could attenuate sodium currents. Moreover, progesterone dose-dependently downregulated Nav1.7 mRNA expression and reduced the sensitivity of TMJ nociception in ovariectomized rats. Furthermore, treatment with progesterone attenuated allodynia of inflamed TMJ in a dose-dependent manner and repressed inflammation-induced Nav1.7 mRNA and protein expression in ovariectomized rats. The progesterone receptor antagonist, RU-486, partially reversed the effect of progesterone on allodynia of inflamed TMJ and TMJ inflammation-induced Nav1.7 mRNA and protein expression. Conclusion:Progesterone, by modulating trigeminal ganglionic Nav1.7, may represent a promising agent to prevent allodynia of inflamed TMJ.
| S-EPMC7399782 | biostudies-literature
Project description:To determine the LncRNA expression profile in dorsal root ganglia tissues of 7 days after rats received 150 μl of CFA (1 mg/ml Mycobacterium tuberculosis, Sigma, USA) through the patella tendon into the right knee joint. CFA injection rats macthed saline injection rats, we uesed LncRNA microArray analysis form Arraystar to examine the expression of LncRNAs and mRNAs in dorsal root ganglia tissues of 7 days after rats received CFA through the patella tendon into the right knee joint and matched Saline through the patella tendon into the right knee joint.
2020-11-12 | GSE146881 | GEO
Project description:BACKGROUND:The proinflammatory cytokine interleukin-1? (IL-1?) drives pain by inducing the expression of inflammatory mediators; however, its ability to regulate sodium channel 1.7 (Nav1.7), a key driver of temporomandibular joint (TMJ) hypernociception, remains unknown. IL-1? induces cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). We previously showed that PGE2 upregulated trigeminal ganglionic Nav1.7 expression. Satellite glial cells (SGCs) involve in inflammatory pain through glial cytokines. Therefore, we explored here in the trigeminal ganglion (TG) whether IL-1? upregulated Nav1.7 expression and whether the IL-1? located in the SGCs upregulated Nav1.7 expression in the neurons contributing to TMJ inflammatory hypernociception. METHODS:We treated rat TG explants with IL-1? with or without inhibitors, including NS398 for COX-2, PF-04418948 for EP2, and H89 and PKI-(6-22)-amide for protein kinase A (PKA), or with adenylate cyclase agonist forskolin, and used real-time PCR, Western blot, and immunohistofluorescence to determine the expressions or locations of Nav1.7, COX-2, cAMP response element-binding protein (CREB) phosphorylation, and IL-1?. We used chromatin immunoprecipitation to examine CREB binding to the Nav1.7 promoter. Finally, we microinjected IL-1? into the TGs or injected complete Freund's adjuvant into TMJs with or without previous microinjection of fluorocitrate, an inhibitor of SGCs activation, into the TGs, and evaluated nociception and gene expressions. Differences between groups were examined by one-way analysis of variance (ANOVA) or independent samples t test. RESULTS:IL-1? upregulated Nav1.7 mRNA and protein expressions in the TG explants, whereas NS398, PF-04418948, H89, or PKI-(6-22)-amide could all block this upregulation, and forskolin could also upregulate Nav1.7 mRNA and protein expressions. IL-1? enhanced CREB binding to the Nav1.7 promoter. Microinjection of IL-1? into the TGs or TMJ inflammation both induced hypernociception of TMJ region and correspondingly upregulated COX-2, phospho-CREB, and Nav1.7 expressions in the TGs. Moreover, microinjection of fluorocitrate into the TGs completely blocked TMJ inflammation-induced activation of SGCs and the upregulation of IL-1? and COX-2 in the SGCs, and phospho-CREB and Nav1.7 in the neurons and alleviated inflammation-induced TMJ hypernociception. CONCLUSIONS:Glial IL-1? upregulated neuronal Nav1.7 expression via the crosstalk between signaling pathways of the glial IL-1?/COX-2/PGE2 and the neuronal EP2/PKA/CREB/Nav1.7 in TG contributing to TMJ inflammatory hypernociception.
| S-EPMC5910598 | biostudies-literature
Project description:Although several underlying pathophysiological processes have been explored, the origin and precise pathomechanism of migraine are still being debated. Inflammatory pathways have been suggested to play role in migraine, trigeminal nociceptor sensitisation, thereby causing hyperalgesia and allodynia. The aim of the present study was to investigate gene expression changes in trigeminal ganglia (TRG), central trigeminal nucleus caudalis (TNC) and peripheral blood mononuclear cells (PBMC) evoked by Complete Freund’s Adjuvant (CFA) induced peripheral inflammation. 512 differentially expressed genes were found between CFA-treated and contralateral TRG samples 7 days after CFA injection. The mRNA expression changes of G-protein coupled receptor 39 (Gpr39), kisspeptin-1 receptor (Kiss1r), kisspeptin (Kiss1) and Lkaaear1 were selected for validation. They were most upregulated on day 3 in TRGs of the CFA-treated side. CFA-induced significant orofacial mechanical allodynia in one day with a maximum on day 3. This correlated with patterns of neuronal (Fosb), glial (Iba1), and astrocyte (Gfap) activation markers in both TRG and TNC, and surprisingly in PBMCs. Similar transcriptional changes of Cgrp, the well-known key molecule in migraine pathophysiology, were also revealed. In TNCs, gene expression changes similar to TRGs were observed but Kiss1r transcripts were not significantly altered while Neurod2 was observed only in TNC. These results could indicate the involvement of Gpr39, Kiss1r and synaptic plasticity associated Lkaaear1, Neurod2 genes in the cascade of events resulting in the sensitization underlying migraine headache and the accompanying facial allodynia.
2018-12-14 | GSE111160 | GEO
Project description:RNA sequencing profiling of mRNAs, lncRNAs and circRNAs in Trigeminal Ganglion following Temporomandibular Joint inflammation
| PRJNA853769 | ENA
Project description:Previous studies have shown that tumor necrosis factor alpha (TNF?) is significantly increased in complete Freund's adjuvant (CFA)-treated temporomandibular joint (TMJ) tissues. However, it is unclear whether TNF? in the trigeminal nociceptive system contributes to the development of TMJ pain. In the present study, we investigated the role of TNF? in trigeminal ganglia (TG) and spinal trigeminal nucleus caudalis (Sp5C) in CFA-induced inflammatory TMJ pain. Intra-TMJ injection of CFA (10 ?l, 5 mg/ml) induced inflammatory pain in the trigeminal nerve V2- and V3-innervated skin areas of WT mice, which was present on day 1 after CFA and persisted for at least 10 days. TNF? in both TG and Sp5C of WT mice was upregulated after CFA injection. The CFA-induced TMJ pain was significantly inhibited in TNF? KO mice. The immunofluorescence staining showed that intra-TMJ CFA injection not only enhanced co-localization of TNF? with Iba1 (a marker for microglia) in both TG and Sp5C but also markedly increased the expression of TNF? in the Sp5C neurons. By the methylated DNA immunoprecipitation assay, we also found that DNA methylation at the TNF gene promoter region in the TG was dramatically diminished after CFA injection, indicating that epigenetic regulation may be involved in the CFA-enhanced TNF? expression in our model. Our results suggest that TNF? in the trigeminal nociceptive system plays a critical role in CFA-induced inflammatory TMJ pain.
| S-EPMC6698364 | biostudies-literature
Project description:Genetic opticospinal EAE (OSE) and MOG-induced EAE (MOG-EAE) are two experimental autoimmune encephalomyelitis (EAE) mouse models of human multiple sclerosis. For the OSE model, double-transgenic 2D2 (TCRMOG) x IgHMOG mice were used. For MOG-EAE, wildtype C57BL/6 mice were immunized with a MOG peptide consisting of the amino acids 35-55, administered in complete Freund’s adjuvant containing 5mg / ml Mycobacterium tuberculosi. The severity of EAE was rated on the scale 0: healthy animal; 1: animal with a flaccid tail; [...]; 4: animal with both hind legs paralyzed. The case groups in the experiment were: OSE1: OSE with disease score 1; OSE4: OSE with disease score 4; MOG4: MOG-EAE injected with both MOG and adjuvant, with disease score 4. The control groups in the experiment were: OSE0: OSE with disease score 0; CFA: C57BL/6 mice injected only with adjuvant (no MOG); WT: Wildtype C57BL/6 mice. The aim of the experiment was to assess gene expression differences 1) between OSE4 and OSE0, 2) between OSE1 and OSE0, and 3) between MOG4 and CFA. For control, WT was compared to OSE0 and CFA. Subsequently, differentially expressed transcripts were compared, first, between the OSE4 vs. OSE0 and the MOG4 vs. CFA contrasts (different EAE models) and, second, between the OSE4 vs. OSE0 and the OSE1 vs. OSE0 contrasts (different EAE severity).
2020-08-21 | E-MTAB-9132 | biostudies-arrayexpress
Project description:In the trigeminal system, disruption of acute resolution processing may lead to uncontrolled inflammation and chronic pain associated with the temporomandibular joint (TMJ). Currently, there are no effective treatments for TMJ pain. Recently, it has been recognized that maresin 1, a newly identified macrophage-derived mediator of inflammation resolution, is a potent analgesic for somatic inflammatory pain without noticeable side effects in mice and a potent endogenous inhibitor of transient receptor potential vanilloid 1 (TRPV1) in the somatic system. However, the molecular mechanisms underlying the analgesic actions of maresin 1 on TMJ pain are unclear in the trigeminal system. Here, by performing TMJ injection of a retrograde labeling tracer DiI (a fluorescent dye), I showed that maresin 1 potently inhibits capsaicin-induced TRPV1 currents and neuronal activity via Gαi-coupled G-protein coupled receptors in DiI-labeled trigeminal nociceptive neurons. Further, maresin 1 blocked TRPV1 agonist-evoked increases in spontaneous excitatory postsynaptic current frequency and abolished TMJ inflammation-induced synaptic plasticity in the trigeminal nucleus. These results demonstrate the potent actions of maresin 1 in regulating TRPV1 in the trigeminal system. Thus, maresin 1 may serve as a novel endogenous inhibitor for treating TMJ-inflammatory pain in the orofacial region.
| S-EPMC4651643 | biostudies-literature