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Advances in Biological Regulation May 2016Somatosensory neurons of the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are responsible for detecting thermal and tactile stimuli. They are also the primary... (Review)
Review
Somatosensory neurons of the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are responsible for detecting thermal and tactile stimuli. They are also the primary neurons mediating pain and itch. A large number of cell surface receptors in these neurons couple to phospholipase C (PLC) enzymes leading to the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and the generation of downstream signaling molecules. These neurons also express many different ion channels, several of which are regulated by phosphoinositides. This review will summarize the knowledge on phosphoinositide signaling in DRG neurons, with special focus on effects on sensory and other ion channels.
Topics: Animals; Calcium; Ganglia, Spinal; Gene Expression Regulation; Humans; Ion Channels; Isoenzymes; Neurons; Pain Perception; Phosphatidylinositol 4,5-Diphosphate; Sensory Thresholds; Signal Transduction; Touch Perception; Trigeminal Ganglion; Type C Phospholipases
PubMed: 26724974
DOI: 10.1016/j.jbior.2015.11.012 -
Neuroscience Bulletin Jan 2021Migraine is a common and debilitating headache disorder. Although its pathogenesis remains elusive, abnormal trigeminal and central nervous system activity is likely to... (Review)
Review
Migraine is a common and debilitating headache disorder. Although its pathogenesis remains elusive, abnormal trigeminal and central nervous system activity is likely to play an important role. Transient receptor potential (TRP) channels, which transduce noxious stimuli into pain signals, are expressed in trigeminal ganglion neurons and brain regions closely associated with the pathophysiology of migraine. In the trigeminal ganglion, TRP channels co-localize with calcitonin gene-related peptide, a neuropeptide crucially implicated in migraine pathophysiology. Many preclinical and clinical data support the roles of TRP channels in migraine. In particular, activation of TRP cation channel V1 has been shown to regulate calcitonin gene-related peptide release from trigeminal nerves. Intriguingly, several effective anti-migraine therapies, including botulinum neurotoxin type A, affect the functions of TRP cation channels. Here, we discuss currently available data regarding the roles of major TRP cation channels in the pathophysiology of migraine and the therapeutic applicability thereof.
Topics: Calcitonin Gene-Related Peptide; Humans; Migraine Disorders; Neurons; Transient Receptor Potential Channels; Trigeminal Ganglion
PubMed: 32870468
DOI: 10.1007/s12264-020-00569-5 -
The Journal of Physiological Sciences :... Sep 2016Peripheral tissue inflammation can alter the properties of somatic sensory pathways, causing behavioral hypersensitivity and resulting in increased responses to pain... (Review)
Review
Peripheral tissue inflammation can alter the properties of somatic sensory pathways, causing behavioral hypersensitivity and resulting in increased responses to pain caused by noxious stimulation (hyperalgesia) and normally innocuous stimulation (allodynia). These hypersensitivities for nociception are caused by changes in the excitability of trigeminal ganglion (TG) neurons. These changes alter sensory information processing in the neurons in the medullary trigeminal nucleus of caudalis. Increasing information is becoming available regarding trigeminal neuron-neuron/neuron-satellite glial cells (SGCs) communication. The activation of intraganglionic communication plays an important role in the creation and maintenance of trigeminal pathological pain. Therefore, in this review, we focus on the recent findings for sensory functions and pharmacological modulation of TG neurons and SGCs under normal and pathological conditions, and we discuss potential therapeutic targets in glia-neuronal interactions for the prevention of trigeminal neuropathic and inflammatory pain.
Topics: Animals; Hyperalgesia; Neurons; Nociception; Pain; Trigeminal Ganglion
PubMed: 27023716
DOI: 10.1007/s12576-016-0448-1 -
Neuron Sep 2005How do migrating neural progenitor cells and growing axons know where to go? In this issue of Neuron, two papers (Knaut et al. and Lieberam et al.) demonstrate that...
How do migrating neural progenitor cells and growing axons know where to go? In this issue of Neuron, two papers (Knaut et al. and Lieberam et al.) demonstrate that activation of Cxcr4 chemokine receptors by the chemokine SDF1/Cxcl12 can direct both of these tasks.
Topics: Animals; Axons; Cell Movement; Chemokine CXCL12; Chemokines; Chemokines, CXC; Mice; Motor Neurons; Neurons, Afferent; Receptors, CXCR4; Signal Transduction; Stem Cells; Trigeminal Ganglion; Zebrafish
PubMed: 16129389
DOI: 10.1016/j.neuron.2005.08.012 -
The Journal of Pain May 2023Temporomandibular disorder (TMD) pain that involves inflammation and injury in the temporomandibular joint (TMJ) and/or masticatory muscle is the most common form of... (Review)
Review
Temporomandibular disorder (TMD) pain that involves inflammation and injury in the temporomandibular joint (TMJ) and/or masticatory muscle is the most common form of orofacial pain. We recently found that transient receptor potential vanilloid-4 (TRPV4) in trigeminal ganglion (TG) neurons is upregulated after TMJ inflammation, and TRPV4 coexpresses with calcitonin gene-related peptide (CGRP) in TMJ-innervating TG neurons. Here, we extended these findings to determine the specific contribution of TRPV4 in TG neurons to TMD pain, and examine whether sensory neuron-TRPV4 modulates TMD pain via CGRP. In mouse models of TMJ inflammation or masseter muscle injury, sensory neuron-Trpv4 conditional knockout (cKO) mice displayed reduced pain. Coexpression of TRPV4 and CGRP in TMJ- or masseter muscle-innervating TG neurons was increased after TMJ inflammation and masseter muscle injury, respectively. Activation of TRPV4-expressing TG neurons triggered secretion of CGRP, which was associated with increased levels of CGRP in peri-TMJ tissues, masseter muscle, spinal trigeminal nucleus, and plasma in both models. Local injection of CGRP into the TMJ or masseter muscle evoked acute pain in naïve mice, while blockade of CGRP receptor attenuated pain in mouse models of TMD. These results suggest that TRPV4 in TG neurons contributes to TMD pain by potentiating CGRP secretion. PERSPECTIVE: This study demonstrates that activation of TRPV4 in TG sensory neurons drives pain by potentiating the release of pain mediator CGRP in mouse models of TMJ inflammation and masseter muscle injury. Targeting TRPV4 and CGRP may be of clinical potential in alleviating TMD pain.
Topics: Mice; Animals; Calcitonin Gene-Related Peptide; TRPV Cation Channels; Temporomandibular Joint Disorders; Sensory Receptor Cells; Facial Pain; Trigeminal Ganglion; Inflammation; Arthritis
PubMed: 36509176
DOI: 10.1016/j.jpain.2022.12.001 -
Acta Neurochirurgica May 2024Based on a personal experience of 4200 surgeries, radiofrequency thermocoagulation is useful lesional treatment for those trigeminal neuralgias (TNs) not amenable to... (Review)
Review
Based on a personal experience of 4200 surgeries, radiofrequency thermocoagulation is useful lesional treatment for those trigeminal neuralgias (TNs) not amenable to microvascular decompression (idiopathic or secondary TNs). Introduced through the foramen ovale, behind the trigemnial ganglion in the triangular plexus, the needle is navigated by radiology and neurophysiological testing to target the retrogasserian fibers corresponding to the trigger zone. Heating to 55-75 °C can achieve hypoesthesia without anaesthesia dolorosa if properly controlled. Depth of anaesthesia varies dynamically sedation for cannulation and lesioning, and awareness during neurophysiologic navigation. Proper technique ensures long-lasting results in more than 75% of patients.
Topics: Trigeminal Neuralgia; Humans; Electrocoagulation; Trigeminal Nerve; Foramen Ovale; Trigeminal Ganglion; Microvascular Decompression Surgery; Treatment Outcome
PubMed: 38727725
DOI: 10.1007/s00701-024-06074-2 -
Journal of Oral Science Mar 2020Nociceptive stimuli to the orofacial region are typically received by the peripheral terminal of trigeminal ganglion (TG) neurons, and noxious orofacial information is...
Nociceptive stimuli to the orofacial region are typically received by the peripheral terminal of trigeminal ganglion (TG) neurons, and noxious orofacial information is subsequently conveyed to the trigeminal spinal subnucleus caudalis and the upper cervical spinal cord (C1-C2). This information is further transmitted to the cortical somatosensory regions and limbic system via the thalamus, which then leads to the perception of pain. It is a well-established fact that the presence of abnormal pain in the orofacial region is etiologically associated with neuroplastic changes that may occur at any point in the pain transmission pathway from the peripheral to the central nervous system (CNS). Recently, several studies have reported that functional plastic changes in a large number of cells, including TG neurons, glial cells (satellite cells, microglia, and astrocytes), and immune cells (macrophages and neutrophils), contribute to the sensitization and disinhibition of neurons in the peripheral and CNS, which results in orofacial pain hypersensitivity.
Topics: Animals; Facial Pain; Microglia; Neuroglia; Rats; Rats, Sprague-Dawley; Trigeminal Ganglion
PubMed: 32132329
DOI: 10.2334/josnusd.19-0373 -
Tissue Engineering. Part C, Methods Aug 2023Corneal nerves originate from the ophthalmic branch of the trigeminal nerve, which enters the cornea at the limbus radially from all directions toward the central...
Corneal nerves originate from the ophthalmic branch of the trigeminal nerve, which enters the cornea at the limbus radially from all directions toward the central cornea. The cell bodies of the sensory neurons of trigeminal nerve are located in the trigeminal ganglion (TG), while the axons are extended into the three divisions, including ophthalmic branch that supplies corneal nerves. Study of primary neuronal cultures established from the TG fibers can therefore provide a knowledge basis for corneal nerve biology and potentially be developed as an platform for drug testing. However, setting up primary neuron cultures from animal TG has been dubious with inconsistency among laboratories due to a lack of efficient isolation protocol, resulting in low yield and heterogenous cultures. In this study, we used a combined enzymatic digestion with collagenase and TrypLE to dissociate mouse TG while preserving nerve cell viability. A subsequent discontinuous Percoll density gradient followed by mitotic inhibitor treatment effectively diminished the contamination of non-neuronal cells. Using this method, we reproducibly generated high yield and homogenous primary TG neuron cultures. Similar efficiency of nerve cell isolation and culture was further obtained for TG tissue cryopreserved for short (1 week) and long duration (3 months), compared to freshly isolated tissues. In conclusion, this optimized protocol shows a promising potential to standardize TG nerve culture and generate a high-quality corneal nerve model for drug testing and neurotoxicity studies.
Topics: Mice; Animals; Trigeminal Ganglion; Neurons; Cornea
PubMed: 37212303
DOI: 10.1089/ten.TEC.2023.0054 -
The Journal of Neuroscience : the... Aug 2019Nociceptors located in the trigeminal ganglion (TG) and DRG are the primary sensors of damaging or potentially damaging stimuli for the head and body, respectively, and...
Nociceptors located in the trigeminal ganglion (TG) and DRG are the primary sensors of damaging or potentially damaging stimuli for the head and body, respectively, and are key drivers of chronic pain states. While nociceptors in these two tissues show a high degree of functional similarity, there are important differences in their development lineages, their functional connections to the CNS, and recent genome-wide analyses of gene expression suggest that they possess some unique genomic signatures. Here, we used translating ribosome affinity purification to comprehensively characterize and compare mRNA translation in -positive nociceptors in the TG and DRG of male and female mice. This unbiased method independently confirms several findings of differences between TG and DRG nociceptors described in the literature but also suggests preferential utilization of key signaling pathways. Most prominently, we provide evidence that translational efficiency in mechanistic target of rapamycin (mTOR)-related genes is higher in the TG compared with DRG, whereas several genes associated with the negative regulator of mTOR, AMP-activated protein kinase, have higher translational efficiency in DRG nociceptors. Using capsaicin as a sensitizing stimulus, we show that behavioral responses are greater in the TG region and this effect is completely reversible with mTOR inhibition. These findings have implications for the relative capacity of these nociceptors to be sensitized upon injury. Together, our data provide a comprehensive, comparative view of transcriptome and translatome activity in TG and DRG nociceptors that enhances our understanding of nociceptor biology. The DRG and trigeminal ganglion (TG) provide sensory information from the body and head, respectively. Nociceptors in these tissues are critical first neurons in the pain pathway. Injury to peripheral neurons in these tissues can cause chronic pain. Interestingly, clinical and preclinical findings support the conclusion that injury to TG neurons is more likely to cause chronic pain and chronic pain in the TG area is more intense and more difficult to treat. We used translating ribosome affinity purification technology to gain new insight into potential differences in the translatomes of DRG and TG neurons. Our findings demonstrate previously unrecognized differences between TG and DRG nociceptors that provide new insight into how injury may differentially drive plasticity states in nociceptors in these two tissues.
Topics: Animals; Female; Ganglia, Spinal; Gene Expression Profiling; Male; Mice; Neurons; Nociceptors; Signal Transduction; Transcriptome; Trigeminal Ganglion
PubMed: 31253755
DOI: 10.1523/JNEUROSCI.2663-18.2019 -
Cell Reports Feb 2023Mechanosensory neurons that innervate the tongue provide essential information to guide feeding, speech, and social grooming. We use in vivo calcium imaging of mouse...
Mechanosensory neurons that innervate the tongue provide essential information to guide feeding, speech, and social grooming. We use in vivo calcium imaging of mouse trigeminal ganglion neurons to identify functional groups of mechanosensory neurons innervating the anterior tongue. These sensory neurons respond to thermal and mechanical stimulation. Analysis of neuronal activity patterns reveal that most mechanosensory trigeminal neurons are tuned to detect moving stimuli across the tongue. Using an unbiased, multilayer hierarchical clustering approach to classify pressure-evoked activity based on temporal response dynamics, we identify five functional classes of mechanosensory neurons with distinct force-response relations and adaptation profiles. These populations are tuned to detect different features of touch. Molecular markers of functionally distinct clusters are identified by analyzing cluster representation in genetically marked neuronal subsets. Collectively, these studies provide a platform for defining the contributions of functionally distinct mechanosensory neurons to oral behaviors crucial for survival in mammals.
Topics: Mice; Animals; Sensory Receptor Cells; Tongue; Trigeminal Ganglion; Touch; Mammals
PubMed: 36763499
DOI: 10.1016/j.celrep.2023.112087