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Cephalalgia : An International Journal... Apr 2018Background The trigeminal ganglion contains neurons that relay sensations of pain, touch, pressure, and many other somatosensory modalities to the central nervous...
Background The trigeminal ganglion contains neurons that relay sensations of pain, touch, pressure, and many other somatosensory modalities to the central nervous system. The ganglion is also a reservoir for latent herpes virus 1 infection. To gain a better understanding of molecular factors contributing to migraine and headache, transcriptome analyses were performed on postmortem human trigeminal ganglia. Methods RNA-Seq measurements of gene expression were conducted on small sub-regions of 16 human trigeminal ganglia. The samples were also characterized for transcripts derived from viral and microbial genomes. Herpes simplex virus 1 (HSV-1) antibodies in blood were measured using the luciferase immunoprecipitation assay. Results Observed molecular heterogeneity could be explained by sampling of anatomically distinct sub-regions of the excised ganglia consistent with neurally-enriched and non-neural, i.e. Schwann cell, enriched subregions. The levels of HSV-1 transcripts detected in trigeminal ganglia correlated with blood levels of HSV-1 antibodies. Multiple migraine susceptibility genes were strongly expressed in neurally-enriched trigeminal samples, while others were expressed in blood vessels. Conclusions These data provide a comprehensive human trigeminal transcriptome and a framework for evaluation of inhomogeneous post-mortem tissues through extensive quality control and refined downstream analyses for RNA-Seq methodologies. Expression profiling of migraine susceptibility genes identified by genetic association appears to emphasize the blood vessel component of the trigeminovascular system. Other genes displayed enriched expression in the trigeminal compared to dorsal root ganglion, and in-depth transcriptomic analysis of the KCNK18 gene underlying familial migraine shows selective neural expression within two specific populations of ganglionic neurons. These data suggest that expression profiling of migraine-associated genes can extend and amplify the underlying neurobiological insights obtained from genetic association studies.
Topics: Adolescent; Adult; Autopsy; Female; Herpesvirus 1, Human; Humans; Male; Middle Aged; Potassium Channels; RNA; Sequence Analysis, RNA; Trigeminal Ganglion; Young Adult
PubMed: 28699403
DOI: 10.1177/0333102417720216 -
Molecular Pain 2018Cooling temperatures and low pH have profound effects on somatosensory functions including nociception. The effects not only can be mediated by cooling temperature...
Cooling temperatures and low pH have profound effects on somatosensory functions including nociception. The effects not only can be mediated by cooling temperature transducers and proton transducers expressed in subpopulations of somatosensory neurons but may also be mediated by ion channels involving membrane excitability such as voltage-dependent K channels in somatosensory neurons. In the present study, we performed the in situ patch-clamp recordings from nociceptive-like trigeminal ganglion neurons in ex vivo trigeminal ganglion preparations of adult rats. We determined effects of cooling temperatures and low pH on membrane properties and voltage-dependent currents in nociceptive-like trigeminal ganglion neurons. Action potential rheobase levels were decreased when nociceptive trigeminal ganglion neurons were cooled from 24°C down to 12°C or when extracellular pH levels were reduced from 7.3 to 6. This indicates that the excitability of nociceptive-like trigeminal ganglion neurons was increased at the cooling temperatures and low pH. The decreases of action potential rheobase levels were accompanied by increases of trigeminal ganglion neuron input resistances at cooling temperatures and low pH, suggesting a possible involvement of background K channels. Cooling temperatures and low pH suppressed voltage-activated inward Na currents and also voltage-dependent outward K currents in nociceptive-like trigeminal ganglion neurons. Voltage-dependent outward K currents in nociceptive-like trigeminal ganglion neurons consist of inactivating A-type K currents and non-inactivating type K currents, and the former were more sensitive to cooling temperatures and low pH. Collectively, suppressing multiple types of K channels may be associated with the enhanced excitability of nociceptive trigeminal ganglion neurons by cooling temperatures and low pH.
Topics: Action Potentials; Animals; Cold Temperature; Hydrogen-Ion Concentration; Male; Membrane Potentials; Nociception; Nociceptors; Potassium Channel Blockers; Rats, Sprague-Dawley; Temperature; Trigeminal Ganglion
PubMed: 30380987
DOI: 10.1177/1744806918814350 -
Current Opinion in Neurobiology Dec 2018The rodent whiskers are topographically mapped in brainstem sensory nuclei as neuronal modules known as barrelettes. Little is known about how the facial whisker pattern... (Review)
Review
The rodent whiskers are topographically mapped in brainstem sensory nuclei as neuronal modules known as barrelettes. Little is known about how the facial whisker pattern is copied into a brainstem barrelette topographic pattern, which serves as a template for the establishment of thalamic barreloid and, in turn, cortical barrel maps, and how precisely is the whisker pattern mapped in the brainstem during prenatal development. Here, we review recent insights advancing our understanding of the intrinsic and extrinsic patterning mechanisms contributing to establish topographical equivalence between the facial whisker pattern and the mouse brainstem during prenatal development and their relative importance.
Topics: Animals; Brain Stem; Fetal Development; Mice; Sensory Receptor Cells; Trigeminal Ganglion; Vibrissae
PubMed: 30342228
DOI: 10.1016/j.conb.2018.09.008 -
Neuroscience Jan 2007Purine receptors have been implicated in central neurotransmission from nociceptive primary afferent neurons, and ATP-mediated currents in sensory neurons have been... (Comparative Study)
Comparative Study
Purine receptors have been implicated in central neurotransmission from nociceptive primary afferent neurons, and ATP-mediated currents in sensory neurons have been shown to be mediated by both P2X3 and P2X2/3 receptors. The aim of the present study was to quantitatively examine the distribution of P2X2 and P2X3 receptors in primary afferent cell bodies in the rat trigeminal ganglion, including those innervating the dura. In order to determine the classes of neurons that express these receptor subtypes, purine receptor immunoreactivity was examined for colocalization with markers of myelinated (neurofilament 200; NF200) or mostly unmyelinated, non-peptidergic fibers (Bandeiraea simplicifolia isolectin B4; IB4). Forty percent of P2X2 and 64% of P2X3 receptor-expressing cells were IB4 positive, and 33% of P2X2 and 31% of P2X3 receptor-expressing cells were NF200 positive. Approximately 40% of cells expressing P2X2 receptors also expressed P2X3 receptors and vice versa. Trigeminal ganglion neurons innervating the dura mater were retrogradely labeled and 52% of these neurons expressed either P2X2 or P2X3 or both receptors. These results are consistent with electrophysiological findings that P2X receptors exist on the central terminals of trigeminal afferent neurons, and provide evidence that afferents supplying the dura express both receptors. In addition, the data suggest specific differences exist in P2X receptor expression between the spinal and trigeminal nociceptive systems.
Topics: Animals; Dura Mater; Immunohistochemistry; Male; Microscopy, Confocal; Nerve Fibers; Neurons; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P2; Receptors, Purinergic P2X2; Receptors, Purinergic P2X3; Trigeminal Ganglion
PubMed: 17110047
DOI: 10.1016/j.neuroscience.2006.09.035 -
The Chinese Journal of Dental Research 2012To assess whether N-methyl-D-aspartate (NMDA) receptor (NR) or oestrogen receptor (OR) expression plays a role in the differences that temporalis muscle afferent fibres...
OBJECTIVE
To assess whether N-methyl-D-aspartate (NMDA) receptor (NR) or oestrogen receptor (OR) expression plays a role in the differences that temporalis muscle afferent fibres are less sensitive to peripheral receptor activation than masseter muscle afferent fibres and do not exhibit sex-related differences in NMDA-evoked discharge.
METHODS
Immunohistochemical techniques were used to examine the expression of NR1, 2A, and 2B subunits of the NMDA receptor in male and female rats and the co-expression of NR2B subunits with ORs in female rats by trigeminal ganglion neurons that innervate the temporalis muscle. In vivo electrophysiological recording methods were employed to assess the response of afferent fibres to injection of NMDA into the temporalis muscle in female rats.
RESULTS
Approximately 20% of temporalis ganglion neurons expressed NR1, NR2A and NR2B subunits, respectively, and there was no sex-related difference in the expression of these subunits. In female rats, both ORα and ORß receptors were identified in the trigeminal ganglion by Western blot. ORs were found on the majority (~80%) of temporalis ganglion neurons that expressed NR2B subunits. A significant positive correlation between blood oestrogen concentration and NMDA-evoked afferent discharge was identified.
CONCLUSION
The absence of sex-related differences in NMDA receptor expression may account for the lack of sex-related differences in NMDA-evoked temporalis afferent discharge. The association of elevated oestrogen concentration with increased afferent response to NMDA and the co-expression of NRs and ORs in temporalis ganglion neurons suggest that sensory input from the temporalis muscle may be modulated by oestrogenic tone.
Topics: Action Potentials; Animals; Electric Stimulation; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogens; Female; Male; Microelectrodes; Neural Conduction; Neurons; Neurons, Afferent; Rats; Rats, Sprague-Dawley; Receptors, Estrogen; Receptors, N-Methyl-D-Aspartate; Sex Factors; Temporal Muscle; Trigeminal Ganglion
PubMed: 23509829
DOI: No ID Found -
BMC Anesthesiology Apr 2022Radiofrequency thermocoagulation of Gasserian ganglion brings with it the difficult problem of how to provide adequate acesodyne therapy for patients in order to make... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Radiofrequency thermocoagulation of Gasserian ganglion brings with it the difficult problem of how to provide adequate acesodyne therapy for patients in order to make the treatment more comfortable. In our study, we assess the safety and efficacy of lidocaine local anesthesia in the treatment of trigeminal neuralgia.
METHODS
From January, 2017 to December, 2020, 80 patients in our hospital who were suffering from trigeminal neuralgia were treated with radiofrequency thermocoagulation through oval foramen. They were all enrolled in our study and randomly divided into a study group and a placebo group. In the study group an appropriate concentration of lidocaine was given outside and inside of the oval foramen after puncturing in place, while in the placebo group the same dose of normal saline was given in the same way. We then recorded the mean arterial pressure (MAP), heart rate (HR) and visual analogue scale (VAS) at different treatment temperatures.
RESULTS
The values of MAP and HR in the study group were generally lower than those in the placebo group, and the difference was statistically significant. Additionally, the two groups showed a significant difference in MAP, HR, and VAS at different treatment temperatures. There were significant differences in MAP and VAS between the study group at the baseline as well as each time point thereafter, and the range of MAP and HR in the study group were lower than those in the placebo group.
CONCLUSION
Reasonable lidocaine local anesthesia can provide analgesic effects and prevent hypertension and arrhythmia during Gasserian ganglion radiofrequency thermocoagulation for the treatment of trigeminal neuralgia.
Topics: Anesthesia, Local; Case-Control Studies; Humans; Lidocaine; Retrospective Studies; Single-Blind Method; Treatment Outcome; Trigeminal Ganglion; Trigeminal Neuralgia
PubMed: 35410169
DOI: 10.1186/s12871-022-01644-2 -
Brain, Behavior, and Immunity Oct 2020Trigeminal neuralgia is often an early symptom of multiple sclerosis (MS), and it generally does not correlate with the severity of the disease. Thus, whether it is...
Glial cell activation and altered metabolic profile in the spinal-trigeminal axis in a rat model of multiple sclerosis associated with the development of trigeminal sensitization.
Trigeminal neuralgia is often an early symptom of multiple sclerosis (MS), and it generally does not correlate with the severity of the disease. Thus, whether it is triggered simply by demyelination in specific central nervous system areas is currently questioned. Our aims were to monitor the development of spontaneous trigeminal pain in an animal model of MS, and to analyze: i) glial cells, namely astrocytes and microglia in the central nervous system and satellite glial cells in the trigeminal ganglion, and ii) metabolic changes in the trigeminal system. The subcutaneous injection of recombinant MOG protein fragment to Dark Agouti male rats led to the development of relapsing-remitting EAE, with a first peak after 13 days, a remission stage from day 16 and a second peak from day 21. Interestingly, orofacial allodynia developed from day 1 post injection, i.e. well before the onset of EAE, and worsened over time, irrespective of the disease phase. Activation of glial cells both in the trigeminal ganglia and in the brainstem, with no signs of demyelination in the latter tissue, was observed along with metabolic alterations in the trigeminal ganglion. Our data show, for the first time, the spontaneous development of trigeminal sensitization before the onset of relapsing-remitting EAE in rats. Additionally, pain is maintained elevated during all stages of the disease, suggesting the existence of parallel mechanisms controlling motor symptoms and orofacial pain, likely involving glial cell activation and metabolic alterations which can contribute to trigger the sensitization of sensory neurons.
Topics: Animals; Facial Pain; Male; Metabolome; Multiple Sclerosis; Neuroglia; Rats; Trigeminal Ganglion
PubMed: 32659316
DOI: 10.1016/j.bbi.2020.07.001 -
Current Protocols in Cell Biology Jun 2019Visualization of dynamic cellular activity has greatly expanded our understanding of brain function. Recently, there has been an increasing number of studies imaging...
Visualization of dynamic cellular activity has greatly expanded our understanding of brain function. Recently, there has been an increasing number of studies imaging rodent brain activity in real time. However, traditional in vivo calcium imaging technology has been limited to superficial brain structures. Because the trigeminal ganglion (TG) is located deep within the cranial cavity of mice, few studies have been able to access to it. To circumvent this limitation, overlying brain tissue must be removed to expose the TG so that optical recording can access deep brain neural ensembles. This unit describes a procedure for conducting non-survival surgery to visualize the TG in live mice. Obtaining large ensembles of direct, real-time readouts of sensory neuron signaling, providing temporal and spatial information across the TG, will help to define the cellular basis of orofacial somatic sensing and pain perception. © 2019 by John Wiley & Sons, Inc.
Topics: Animals; Brain Mapping; Mice; Neurosurgical Procedures; Pain Perception; Trigeminal Ganglion
PubMed: 30724481
DOI: 10.1002/cpcb.84 -
The Journal of Headache and Pain Jan 2022Clinical observations suggest that hyperinsulinemia and insulin resistance can be associated with migraine headache. In the present study we examined the effect of...
BACKGROUND
Clinical observations suggest that hyperinsulinemia and insulin resistance can be associated with migraine headache. In the present study we examined the effect of insulin on transient receptor potential vanilloid 1 (TRPV1) receptor-dependent meningeal nociceptor functions in rats.
METHODS
The effects of insulin on the TRPV1 receptor stimulation-induced release of calcitonin gene related peptide (CGRP) from trigeminal afferents and changes in meningeal blood flow were studied. Colocalization of the insulin receptor, the TRPV1 receptor and CGRP was also analyzed in trigeminal ganglion neurons.
RESULTS
Insulin induced release of CGRP from meningeal afferents and consequent increases in dural blood flow through the activation of TRPV1 receptors of trigeminal afferents. Insulin sensitized both neural and vascular TRPV1 receptors making them more susceptible to the receptor agonist capsaicin. Immunohistochemistry revealed colocalization of the insulin receptor with the TRPV1 receptor and CGRP in a significant proportion of trigeminal ganglion neurons.
CONCLUSIONS
Insulin may activate or sensitize meningeal nociceptors that may lead to enhanced headache susceptibility in persons with increased plasma insulin concentration.
Topics: Animals; Calcitonin Gene-Related Peptide; Capsaicin; Insulin; Rats; TRPV Cation Channels; Trigeminal Ganglion
PubMed: 35033025
DOI: 10.1186/s10194-021-01380-x -
Neuropeptides Dec 2023Binding of brain-derived neurotrophic factor (BDNF) to its receptor tyrosine kinase B (TrkB) is essential for the development of the hippocampus, which regulates memory...
Binding of brain-derived neurotrophic factor (BDNF) to its receptor tyrosine kinase B (TrkB) is essential for the development of the hippocampus, which regulates memory and learning. Decreased masticatory stimulation during growth reportedly increases BDNF expression while decreasing TrkB expression in the hippocampus. Increased BDNF expression is associated with Wnt family member 3A (Wnt3a) expression and decreased expression of Rho GTPase Activating Protein 33 (ARHGAP33), which regulates intracellular transport of TrkB. TrkB expression may be decreased at the cell surface and affects the hippocampus via BDNF/TrkB signaling. Mastication affects cerebral blood flow and the neural cascade that occurs through the trigeminal nerve and hippocampus. In the current study, we hypothesized that decreased masticatory stimulation reduces memory/learning in mice due to altered Wnt3a and ARHGAP33 expression, which are related to memory/learning functions in the hippocampus. To test this hypothesis, we fed mice a powdered diet until 14 weeks of age and analyzed the BDNF and TrkB mRNA expression in the right hippocampus using real-time polymerase chain reaction and Wnt3a and ARHGAP33 levels in the left hippocampus using western blotting. Furthermore, we used staining to assess BDNF and TrkB expression in the hippocampus and the number of nerve cells, the average size of each single cell and the area of intercellular spaces of the trigeminal ganglion (TG). We found that decreased masticatory stimulation affected the expression of BDNF, Wnt3a, ARHGAP33, and TrkB proteins in the hippocampus, as well as memory/learning. The experimental group showed significantly decreased numbers of neurons and increased the area of intercellular spaces in the TG. Our findings suggest that reduced masticatory stimulation during growth induces a decline in memory/learning by modulating molecular transmission mechanisms in the hippocampus and TG.
Topics: Mice; Animals; Brain-Derived Neurotrophic Factor; Trigeminal Ganglion; Wnt Signaling Pathway; Mastication; Receptor, trkB; Cognition; Hippocampus
PubMed: 37634443
DOI: 10.1016/j.npep.2023.102370