Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.738
Filtrar
1.
J Biomed Nanotechnol ; 17(7): 1371-1379, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34446140

RESUMO

Occlusal trauma (OT), by causing periodontal tissue damage, can activate and enhance the activity of the peripheral and central nervous system (CNS) neuropeptides. The brain-derived neurotrophic factor (BDNF) gene is activity-dependent and exhibits marked alterations, characterized by protection against injury and repair. Our results show the possible molecular mechanism through which noxious environmental stimuli induce alterations in BDNF activity in the local periodontal tissue, the primary sensory neurons-Vc, and the hippocampus, suggesting systemic impairment. BDNF serves a more positive and enduring trauma protection and repair function in Vc compared to that in local dental tissue.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Oclusão Dentária Traumática , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Humanos , Periodonto/metabolismo , Núcleos do Trigêmeo/metabolismo
2.
J Headache Pain ; 22(1): 86, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34325647

RESUMO

BACKGROUND: Central sensitization is considered a critical pathogenic mechanism of chronic migraine (CM). Activation of microglia in the trigeminal nucleus caudalis (TNC) contributes to this progression. Microglial glucagon-like peptide-1 receptor (GLP-1R) activation can alleviate pain; however, whether it is involved in the mechanism of CM has not been determined. Thus, this study aims to investigate the precise role of GLP-1R in the central sensitization of CM. METHODS: Repeated nitroglycerin injection-treated mice were used as a CM animal model in the experiment. To identify the distribution and cell localization of GLP-1R in the TNC, we performed immunofluorescence staining. Changes in the expression of GLP-1R, Iba-1, PI3K and p-Akt in the TNC were examined by western blotting. To confirm the effect of GLP-1R and PI3K/Akt in CM, a GLP-1R selective agonist (liraglutide) and antagonist (exendin(9-39)) and a PI3K selective antagonist (LY294002) were administered. Mechanical hypersensitivity was measured through von Frey filaments. To investigate the role of GLP-1R in central sensitization, calcitonin gene-related peptide (CGRP) and c-fos were determined using western blotting and immunofluorescence. To determine the changes in microglial activation, IL-1ß and TNF-α were examined by western blotting, and the number and morphology of microglia were measured by immunofluorescence. We also confirmed the effect of GLP-1R on microglial activation in lipopolysaccharide-treated BV-2 microglia. RESULTS: The protein expression of GLP-1R was increased in the TNC after nitroglycerin injection. GLP-1R was colocalized with microglia and astrocytes in the TNC and was fully expressed in BV-2 microglia. The GLP-1R agonist liraglutide alleviated basal allodynia and suppressed the upregulation of CGRP, c-fos and PI3K/p-Akt in the TNC. Similarly, the PI3K inhibitor LY294002 prevented nitroglycerin-induced hyperalgesia. In addition, activating GLP-1R reduced Iba-1, IL-1ß and TNF-α release and inhibited TNC microglial number and morphological changes (process retraction) following nitroglycerin administration. In vitro, the protein levels of IL-1ß and TNF-α in lipopolysaccharide-stimulated BV-2 microglia were also decreased by liraglutide. CONCLUSIONS: These findings suggest that microglial GLP-1R activation in the TNC may suppress the central sensitization of CM by regulating TNC microglial activation via the PI3K/Akt pathway.


Assuntos
Sensibilização do Sistema Nervoso Central , Transtornos de Enxaqueca , Animais , Receptor do Peptídeo Semelhante ao Glucagon 1 , Camundongos , Microglia , Transtornos de Enxaqueca/induzido quimicamente , Transtornos de Enxaqueca/tratamento farmacológico , Nitroglicerina/farmacologia , Fosfatidilinositol 3-Quinases , Núcleos do Trigêmeo
3.
PLoS One ; 16(6): e0252943, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34111171

RESUMO

The extent to which a nasal whiff of scent can exogenously orient visual spatial attention remains poorly understood in humans. In a series of seven studies, we investigated the existence of an exogenous capture of visual spatial attention by purely trigeminal (i.e., CO2) and both olfactory and trigeminal stimuli (i.e., eucalyptol). We chose these stimuli because they activate the trigeminal system which can be considered as an alert system and are thus supposedly relevant for the individual, and thus prone to capture attention. We used them as lateralized cues in a variant of a visual spatial cueing paradigm. In valid trials, trigeminal cues and visual targets were presented on the same side whereas in invalid trials they were presented on opposite sides. To characterize the dynamics of the cross-modal attentional capture, we manipulated the interval between the onset of the trigeminal cues and the visual targets (from 580 to 1870 ms). Reaction times in trigeminal valid trials were shorter than all other trials, but only when this interval was around 680 or 1170 ms for CO2 and around 610 ms for eucalyptol. This result reflects that both pure trigeminal and olfactory-trigeminal stimuli can exogenously capture humans' spatial visual attention. We discuss the importance of considering the dynamics of this cross-modal attentional capture.


Assuntos
Atenção/fisiologia , Odorantes/análise , Bulbo Olfatório/fisiologia , Navegação Espacial/fisiologia , Núcleos do Trigêmeo/fisiologia , Adulto , Dióxido de Carbono/análise , Sinais (Psicologia) , Eucaliptol/análise , Humanos , Percepção Olfatória , Estimulação Luminosa , Tempo de Reação/fisiologia , Adulto Jovem
4.
Med Hypotheses ; 153: 110626, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34130114

RESUMO

Primary sensory neurons are usually situated in ganglia outside the brain, while the mesencephalic nucleus of the trigeminal nerve (Me5) is situated inside the brain. However, it remains unknown why only Me5 situated inside the brain is. The neurons of Me5 are the cell bodies of primary afferent fibers concerned with the muscles of mastication and periodontal receptors of both maxillary and mandibular teeth. Interestingly, there was no Me5 till the evolution level of the agnatha, vertebrates which lack jaws, while Me5 appeared with the evolution of jawed vertebrates, the gnathostomes. Thus, I speculate that the appearance of jaws necessitated the emergence of a novel sensory system including newly-made primary sensory neurons to co-ordinate jaw movement and this need was met by the appearance of Me5. Although primary sensory neurons are usually generated from the neural crest or the neurogenic placodes, primary sensory neurons in Me5 are derived from neuroepithelium of the dorsal midline of the midbrain. Taken together, I propose the following hypothesis; (1) Me5 did not exist till the evolution level of agnatha, which lacks jaw. (2) When jawed vertebrates evolved, a new sensory system including new primary sensory neurons for mastication was needed. (3) At that point, there was no capacity for the neural crest and neurogenic placodes to make primary sensory neurons. (4) However, there remained capacity only for the neuroepithelium of the midbrain to make primary sensory neurons. (5) Thus, Me5 was newly made inside the CNS.


Assuntos
Mesencéfalo , Núcleos do Trigêmeo , Animais , Axônios , Neurônios , Nervo Trigêmeo
5.
Eur J Oral Sci ; 129(4): e12788, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33945647

RESUMO

Occlusion has been proposed to play a role for body posture and balance, both of which are mediated mainly by the cerebellum. The dorsomedial part of the principal sensory trigeminal nucleus (Vpdm) has direct projection to the cerebellum. The experimental unilateral anterior crossbite (UAC) has an impact on the motor nuclei in the brain stem via trigeminal mesencephalic nucleus (Vme). The current aim was to explore whether UAC has an impact on Vpdm-cerebellum circuit. The inferior alveolar nerve was injected into cholera toxin B subunit (CTb), the cerebellum was injected into fluoro-gold (FG), and the Vpdm was injected into biotinylated dextran amine (BDA) to identify the activation of Vpdm-cerebellum circuit by UAC. Data indicated that there were more neuronal nuclei (NeuN)/CTb/FG triple-labelled neurons and NeuN/CTb/vesicular glutamate transporter 1(VGLUT1) triple-labelled neurons in the Vpdm, and more NeuN/BDA/ VGLUT1 triple-labelled neurons in the cerebellum of rats with UAC than in control rats. The VGLUT1 expression in the Vpdm and cerebellum in the UAC group was higher than that in control rats. These findings indicate an excitatory impact of UAC on the Vpdm-cerebellum pathway and support the role of occlusion for body posture and balance.


Assuntos
Má Oclusão , Núcleos do Trigêmeo , Animais , Neurônios/metabolismo , Ratos , Núcleos do Trigêmeo/metabolismo , Proteína Vesicular 1 de Transporte de Glutamato/metabolismo
6.
J Headache Pain ; 22(1): 17, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33789568

RESUMO

BACKGROUND: The topical inflammatory soup can model the inflammation of the dura mater causing hypersensitivity and activation of the trigeminal system, a phenomenon present in migraineurs. Calcitonin gene-related peptide, transient receptor potential vanilloid-1 receptor, and neuronal nitric oxide synthase are important in the sensitization process there. 5-HT1B/1D receptor agonists, triptans are used as a treatment of migraine. Kynurenic acid an NMDA antagonist can act on structures involved in trigeminal activation. AIM: We investigated the effect of inflammatory soup induced dural inflammation on the calcitonin gene-related peptide, transient receptor potential vanilloid-1 receptor, and neuronal nitric oxide synthase levels in the caudal trigeminal nucleus. We also tested whether pretreatment with a well-known antimigraine drug, such as sumatriptan and kynurenic acid, a compound with a different mechanism of action, can affect these changes and if their modulatory effects are comparable. MATERIAL AND METHODS: After subcutaneous sumatriptan or intraperitoneal kynurenic acid the dura mater of adult male Sprague-Dawley rats (n = 72) was treated with inflammatory soup or its vehicle (synthetic interstitial fluid). Two and a half or four hours later perfusion was performed and the caudal trigeminal nucleus was removed for immunohistochemistry. RESULTS AND CONCLUSION: Inflammatory soup increased calcitonin gene-related peptide, transient receptor potential vanilloid-1 receptor, and neuronal nitric oxide synthase in the caudal trigeminal nucleus compared to placebo, which was attenuated by sumatriptan and kynurenic acid. This suggests the involvement of 5-HT1B/1D and NMDA receptors in neurogenic inflammation development of the dura and thus in migraine attacks.


Assuntos
Sumatriptana , Núcleo Inferior Caudal do Nervo Trigêmeo , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Dura-Máter/metabolismo , Ácido Cinurênico , Masculino , Ratos , Ratos Sprague-Dawley , Sumatriptana/farmacologia , Núcleo Inferior Caudal do Nervo Trigêmeo/metabolismo , Núcleos do Trigêmeo
7.
Proc Natl Acad Sci U S A ; 118(11)2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33688051

RESUMO

For neuronal circuits in the brain to mature, necessary synapses must be maintained and redundant synapses eliminated through experience-dependent mechanisms. However, the functional differentiation of these synapse types during the refinement process remains elusive. Here, we addressed this issue by distinct labeling and direct recordings of presynaptic terminals fated for survival and for elimination in the somatosensory thalamus. At surviving terminals, the number of total releasable vesicles was first enlarged, and then calcium channels and fast-releasing synaptic vesicles were tightly coupled in an experience-dependent manner. By contrast, transmitter release mechanisms did not mature at terminals fated for elimination, irrespective of sensory experience. Nonetheless, terminals fated for survival and for elimination both exhibited developmental shortening of action potential waveforms that was experience independent. Thus, we dissected experience-dependent and -independent developmental maturation processes of surviving and eliminated presynaptic terminals during neuronal circuit refinement.


Assuntos
Terminações Pré-Sinápticas/fisiologia , Potenciais de Ação , Vias Aferentes/fisiologia , Animais , Canais de Cálcio/metabolismo , Camundongos , Rede Nervosa/fisiologia , Neurotransmissores/metabolismo , Vesículas Sinápticas/metabolismo , Núcleos do Trigêmeo/fisiologia , Núcleos Ventrais do Tálamo/fisiologia , Vibrissas/inervação , Vibrissas/fisiologia
8.
J Neurophysiol ; 125(4): 1517-1531, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33689491

RESUMO

The rat whisker system connects the tactile environment with the somatosensory thalamocortical system using only two synaptic stages. Encoding properties of the first stage, the primary afferents with somas in the trigeminal ganglion (TG), has been well studied, whereas much less is known from the second stage, the brainstem trigeminal nuclei (TN). The TN are a computational hub giving rise to parallel ascending tactile pathways and receiving feedback from many brain sites. We asked the question, whether encoding properties of TG neurons are kept by two trigeminal nuclei, the principalis (Pr5) and the spinalis interpolaris (Sp5i), respectively giving rise to two "lemniscal" and two "nonlemniscal" pathways. Single units were recorded in anesthetized rats while a single whisker was deflected on a band-limited white noise trajectory. Using information theoretic methods and spike-triggered mixture models (STM), we found that both nuclei encode the stimulus locally in time, i.e., stimulus features more than 10 ms in the past do not significantly influence spike generation. They further encode stimulus kinematics in multiple, distinct response fields, indicating encoding characteristics beyond previously described directional responses. Compared with TG, Pr5 and Sp5i gave rise to lower spike and information rates, but information rate per spike was on par with TG. Importantly, both brainstem nuclei were found to largely keep encoding properties of primary afferents, i.e. local encoding and kinematic response fields. The preservation of encoding properties in channels assumed to serve different functions seems surprising. We discuss the possibility that it might reflect specific constraints of frictional whisker contact with object surfaces.NEW & NOTEWORTHY We studied two trigeminal nuclei containing the second neuron on the tactile pathway of whisker-related tactile information in rats. We found that the subnuclei, traditionally assumed to give rise to functional tactile channels, nevertheless transfer primary afferent information with quite similar properties in terms of integration time and kinematic profile. We discuss whether such commonality may be due the requirement to adapt to physical constraints of frictional whisker contact.


Assuntos
Fenômenos Eletrofisiológicos/fisiologia , Neurônios Aferentes/fisiologia , Percepção do Tato/fisiologia , Núcleos do Trigêmeo/fisiologia , Vibrissas/fisiologia , Vias Aferentes/fisiologia , Animais , Fenômenos Biomecânicos , Ratos , Fatores de Tempo
9.
Neuroreport ; 32(2): 144-156, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33395186

RESUMO

Although the mechanism of chronic migraine is still unclear, more and more studies have shown that mitochondrial dysfunction plays a possible role in migraine pathophysiology. Silent information regulator 1 (SIRT1) plays a vital role in mitochondrial dysfunction in many diseases. However, there is no research on the role of SIRT1 in mitochondrial dysfunction of chronic migraine. The aim of this study was to explore the role of SIRT1 in mitochondrial dysfunction in chronic migraine. A rat model was established through repeated dural infusions of inflammatory soup for 7 days to simulate chronic migraine attacks. Cutaneous hyperalgesia caused by the repeated infusions of inflammatory soup was detected using the von Frey test. Then, we detected SIRT1 expression in the trigeminal nucleus caudalis. To explore the effect of SIRT1 on mitochondrial dysfunction in chronic migraine rats, we examined whether SRT1720, an activator of SIRT1, altered mitochondrial dysfunction in chronic migraine rats. Repeated infusions of inflammatory soup resulted in cutaneous hyperalgesia accompanied by downregulation of SIRT1. SRT1720 significantly alleviated the cutaneous hyperalgesia induced by repeated infusions of inflammatory soup. Furthermore, activation of SIRT1 markedly increased the expression of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha, transcription factor A, nuclear respiratory factor 1 and nuclear respiratory factor 2 mitochondrial DNA and increased the ATP content and mitochondrial membrane potential. Our results indicate that SIRT1 may have an effect on mitochondrial dysfunction in chronic migraine rats. Activation of SIRT1 has a protective effect on mitochondrial function in chronic migraine rats.


Assuntos
Transtornos de Enxaqueca/genética , Mitocôndrias/metabolismo , Neurônios/metabolismo , Sirtuína 1/genética , Núcleos do Trigêmeo/metabolismo , Animais , Western Blotting , DNA Mitocondrial/metabolismo , Transtornos de Enxaqueca/metabolismo , Mitocôndrias/ultraestrutura , Fator 1 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/ultraestrutura , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Ratos , Fatores de Transcrição/metabolismo , Núcleos do Trigêmeo/citologia , Núcleos do Trigêmeo/ultraestrutura , Regulação para Cima
10.
Brain Struct Funct ; 226(3): 889-900, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33475854

RESUMO

Detailed information about the development of excitatory and inhibitory synapses on the genioglossal (GG) motoneuron may help to understand the mechanism of fine control of GG motoneuron firing and the coordinated tongue movement during postnatal development. For this, we investigated the development of γ-aminobutyric acid (GABA)-immunopositive (GABA +), glycine + (Gly +), and glutamate + (Glut +) axon terminals (boutons) on the somata of rat GG motoneurons at a postnatal day 2 (P2), P6 and P18 by retrograde labeling of GG motoneurons with horseradish peroxidase, electron microscopic postembedding immunogold staining with GABA, Gly, and Glut antisera, and quantitative analysis. The number of boutons per GG motoneuron somata and the mean length of bouton apposition, measures of bouton size and synaptic covering percentage, were significantly increased from P2/P6 to P18. The number and fraction of GABA + only boutons of all boutons decreased significantly, whereas those of Gly + only boutons increased significantly from P2/P6 to P18, suggesting developmental switch from GABAergic to glycinergic synaptic transmission. The fraction of mixed GABA +/Gly + boutons of all boutons was the highest among inhibitory bouton types throughout the postnatal development. The fractions of excitatory and inhibitory boutons of all boutons remained unchanged during postnatal development. These findings reveal a distinct developmental pattern of inhibitory synapses on the GG motoneurons different from that on spinal or trigeminal motoneurons, which may have an important role in the regulation of the precise and coordinated movements of the tongue during the maturation of the oral motor system.


Assuntos
Dendritos/ultraestrutura , Ácido Glutâmico/metabolismo , Neurônios Motores/ultraestrutura , Terminações Pré-Sinápticas/ultraestrutura , Animais , Masculino , Microscopia Eletrônica/métodos , Neurônios Motores/fisiologia , Inibição Neural/fisiologia , Ratos Sprague-Dawley , Sinapses/fisiologia , Núcleos do Trigêmeo/ultraestrutura , Ácido gama-Aminobutírico/metabolismo
11.
Neurosci Lett ; 738: 135400, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979458

RESUMO

The interneuronal system in the brainstem reticular formation plays an important role in elaborate muscle coordination during various orofacial motor behaviors. In this study, we examined the distribution in the brainstem reticular formation of the sites that induce monosynaptic motor activity in the mylohyoid (jaw-opening) and hypoglossal nerves using an arterially perfused rat preparation. Electrical stimulation applied to 286 and 247 of the 309 sites in the brainstem evoked neural activity in the mylohyoid and hypoglossal nerves, respectively. The mean latency of the first component in the mylohyoid nerve response was significantly shorter than that in the hypoglossal nerve response. Moreover, the latency histogram of the first component in the hypoglossal nerve responses was bimodal, which was separated by 4.0 ms. The sites that induced short-latency (<4.0 ms) motor activity in the mylohyoid nerve and the hypoglossal nerve were frequently distributed in the rostral portion and the caudal portion of the brainstem reticular formation, respectively. Such difference in distributions of short-latency sites for mylohyoid and hypoglossal nerve responses likely corresponds to the distribution of excitatory premotor neurons targeting mylohyoid and hypoglossal motoneurons.


Assuntos
Tronco Encefálico/fisiologia , Estimulação Elétrica , Nervo Hipoglosso/patologia , Nervo Hipoglosso/fisiologia , Formação Reticular/fisiologia , Animais , Tronco Encefálico/patologia , Estimulação Elétrica/métodos , Eletromiografia/métodos , Neurônios Motores/fisiologia , Ratos , Formação Reticular/patologia , Núcleos do Trigêmeo/patologia , Núcleos do Trigêmeo/fisiologia
12.
Neuropharmacology ; 178: 107981, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32745488

RESUMO

This study aims to explore whether orexin 1 receptors (Orx1R) in the ventrolateral periaqueductal gray matter (vlPAG) play a role in the modulation of migraine headaches in adult male Wistar rats. To model chronic migraine-associated pain, nitroglycerin (NTG) (5 mg/kg/IP) was administered to test subjects every second day for 9 days. After the last NTG injection, rats were randomly separated into the following groups (n = 6): orexin-A (OrxA) groups that received intra-vlPAG OrxA (25, 50, and 100 pM), an Orx1R antagonist group, a SB-334867 (20 µM) group; and a SB-334867 (20 µM) + OrxA (100 pM) group. After 10 min, migraine-associated behavioral symptoms were recorded in all animals for up to 90 min. Light-dark chamber and hot plate tests were used for assessing light aversion and thermal hyperalgesia, respectively. Calcitonin gene-related peptide (CGRP)-positive cells were detected in the trigeminal nucleus caudalis (Vc) by immunofluorescence microscopy. NTG caused significant freezing behavior, which was prevented by all OrxA doses. Moreover, OrxA (100 pM) could obstruct NTG-induced increases in facial rubbing and decreases in climbing and body grooming. Furthermore, NTG-induced light aversion and thermal hyperalgesia were attenuated by OrxA at doses of 50 and 100 pM. The effects of OrxA were significantly blocked by SB-334867 (20 µM). Besides, OrxA (100 pM) decreased NTG-induced CGRP upregulation. The data revealed that the activation of Orx1Rs in the vlPAG is effective in relieving NTG-induced migraine symptoms mainly by the downregulation of CGRP in the Vc of rats.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Transtornos de Enxaqueca/metabolismo , Nitroglicerina/toxicidade , Receptores de Orexina/metabolismo , Substância Cinzenta Periaquedutal/metabolismo , Núcleos do Trigêmeo/metabolismo , Animais , Benzoxazóis/administração & dosagem , Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores , Masculino , Microinjeções/métodos , Transtornos de Enxaqueca/induzido quimicamente , Transtornos de Enxaqueca/prevenção & controle , Naftiridinas/administração & dosagem , Antagonistas dos Receptores de Orexina/administração & dosagem , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Ratos , Ratos Wistar , Núcleos do Trigêmeo/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia , Ureia/administração & dosagem , Ureia/análogos & derivados
13.
Eur Rev Med Pharmacol Sci ; 24(13): 7399-7411, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32706079

RESUMO

OBJECTIVE: The efficacy of melatonin as an analgesic agent has been well documented in animals and humans. However, the underlying mechanisms by which melatonin exerts antinociceptive effects on inflammatory pain are poorly understood. Here, we investigated the potential of melatonin to ameliorate inflammatory pain. MATERIALS AND METHODS: In vitro, ND7/23 neurons were treated with capsaicin. We used PCR and Western blot analyses to detect the expression of neuronal nitric oxide synthase (nNOS) in response to melatonin. Orofacial inflammatory pain was induced by 4% formalin administration on the right whisker pad of Sprague Dawley (SD) rats. The analgesic effect of melatonin was evaluated using mechanical threshold analyses. The expression level of nNOS in the trigeminal ganglion (TG) and trigeminal nucleus caudalis (Vc) neurons was assessed by RNAscope and immunohistochemistry. RESULTS: In vitro, capsaicin upregulated the expression of nNOS, which was dose-dependently reversed by melatonin pretreatment (p < 0.001). In a rat model of orofacial inflammatory pain, melatonin pretreatment significantly attenuated mechanical allodynia in both the acute and chronic phases (p < 0.05). Furthermore, melatonin decreased the formalin-evoked elevated nNOS mRNA and protein levels in the TG and Vc neurons in the acute and chronic phases (p < 0.05). CONCLUSIONS: Taken together, these results suggest that nNOS may play an active role in both peripheral and central processing of nociceptive information following orofacial inflammatory pain induction. The regulatory effect of melatonin on nNOS in inflammatory pain may have potential implications for the development of novel analgesic strategies.


Assuntos
Analgésicos/farmacologia , Dor Facial/prevenção & controle , Hiperalgesia/prevenção & controle , Melatonina/farmacologia , Óxido Nítrico Sintase Tipo I/metabolismo , Dor Nociceptiva/prevenção & controle , Limiar da Dor/efeitos dos fármacos , Células Receptoras Sensoriais/efeitos dos fármacos , Gânglio Trigeminal/efeitos dos fármacos , Núcleos do Trigêmeo/efeitos dos fármacos , Animais , Linhagem Celular , Modelos Animais de Doenças , Dor Facial/enzimologia , Dor Facial/fisiopatologia , Hiperalgesia/enzimologia , Hiperalgesia/fisiopatologia , Dor Nociceptiva/enzimologia , Dor Nociceptiva/fisiopatologia , Ratos Sprague-Dawley , Células Receptoras Sensoriais/enzimologia , Gânglio Trigeminal/metabolismo , Gânglio Trigeminal/fisiopatologia , Núcleos do Trigêmeo/enzimologia , Núcleos do Trigêmeo/fisiopatologia
14.
Chem Senses ; 45(7): 573-579, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-32572463

RESUMO

Exposure of the oral cavity to acidic solutions evokes not only a sensation of sour, but also of sharp or tangy. Acidic substances potentially stimulate both taste buds and acid-sensitive mucosal free nerve endings. Mice lacking taste function (P2X2/P2X3 double-KO mice) refuse acidic solutions similar to wildtype (WT) mice and intraoral infusion of acidic solutions in these KO animals evokes substantial c-Fos activity within orosensory trigeminal nuclei as well as of the nucleus of the solitary tract (nTS) (Stratford, Thompson, et al. 2017). This residual acid-evoked, non-taste activity includes areas that receive inputs from trigeminal and glossopharyngeal peptidergic (CGRP-containing) nerve fibers that express TrpA1 and TrpV1 both of which are activated by low pH. We compared avoidance responses in WT and TrpA1/V1 double-KO (TRPA1/V1Dbl-/-) mice in brief-access behavioral assay (lickometer) to 1, 3, 10, and 30 mM citric acid, along with 100 µM SC45647 and H2O. Both WT and TRPA1/V1Dbl-/- show similar avoidance, including to higher concentrations of citric acid (10 and 30 mM; pH 2.62 and pH 2.36, respectively), indicating that neither TrpA1 nor TrpV1 is necessary for the acid-avoidance behavior in animals with an intact taste system. Similarly, induction of c-Fos in the nTS and dorsomedial spinal trigeminal nucleus was similar in the WT and TRPA1/V1Dbl-/- animals. Taken together these results suggest non-TrpV1 and non-TrpA1 receptors underlie the residual responses to acids in mice lacking taste function.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Ácido Cítrico/farmacologia , Canal de Cátion TRPA1/genética , Canais de Cátion TRPV/genética , Animais , Aprendizagem da Esquiva/fisiologia , Ácido Cítrico/química , Feminino , Guanidinas/química , Guanidinas/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Proto-Oncogênicas c-fos/metabolismo , Núcleo Solitário/metabolismo , Canal de Cátion TRPA1/deficiência , Canais de Cátion TRPV/deficiência , Núcleos do Trigêmeo/metabolismo
15.
Mol Brain ; 13(1): 67, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32370769

RESUMO

The linear nucleus (Li) was identified in 1978 from its projections to the cerebellum. However, there is no systematic study of its connections with other areas of the central nervous system possibly due to the challenge of injecting retrograde tracers into this nucleus. The present study examines its afferents from some nuclei involved in motor and cardiovascular control with anterograde tracer injections. BDA injections into the central amygdaloid nucleus result in labeled fibers to the ipsilateral Li. Bilateral projections with an ipsilateral dominance were observed after injections in a) jointly the paralemniscal nucleus, the noradrenergic group 7/ Köllike -Fuse nucleus/subcoeruleus nucleus, b) the gigantocellular reticular nucleus, c) and the solitary nucleus/the parvicellular/intermediate reticular nucleus. Retrogradely labeled neurons were observed in Li after BDA injections into all these nuclei except the central amygdaloid and the paralemniscal nuclei. Our results suggest that Li is involved in a variety of physiological functions apart from motor and balance control it may exert via its cerebellar projections.


Assuntos
Biotina/análogos & derivados , Dextranos/farmacologia , Núcleo Dorsal da Rafe/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Vias Aferentes , Tonsila do Cerebelo/citologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Animais , Biotina/farmacologia , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Núcleo Dorsal da Rafe/citologia , Núcleo Dorsal da Rafe/metabolismo , Bulbo/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Vias Neurais/efeitos dos fármacos , Vias Neurais/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Tegmento Pontino/citologia , Tegmento Pontino/efeitos dos fármacos , Tegmento Pontino/metabolismo , Núcleos do Trigêmeo/citologia , Núcleos do Trigêmeo/efeitos dos fármacos , Núcleos do Trigêmeo/metabolismo , Núcleos Vestibulares/citologia , Núcleos Vestibulares/efeitos dos fármacos , Núcleos Vestibulares/metabolismo
16.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 55(4): 259-263, 2020 Apr 09.
Artigo em Chinês | MEDLINE | ID: mdl-32268626

RESUMO

Objective: To determine the opening and closing action of the external muscle, the projection pathway of the axon terminal of trigeminal motor nucleus (Vmo) neuron to the lateral pterygoid muscle was revealed. Methods: In this study, 10 SD rats of 8 weeks old were included. The left lateral pterygoid muscle of SD rats was surgically exposed, and the wound was closed after intramuscular injection of hydroxystilbamidine/fluorogold (FG) 3-5 µl. Seven days after the operation, the experimental animals were perfused, samples collected and sectioned for immunofluorescence staining. After FG injection into the lateral pterygoid muscle, the FG reversed in the Vmo neurons. Results: In the Vmo neurons on the FG injection side (left side), a large number of FG reversed neurons were found in the corpus luteum and dendrites. These neurons were not only distributed in the dorsolateral part of the trigeminal motor nucleus that innervated the closed muscle, but also in the ventral medial portion of the trigeminal nucleus of the open muscle. Conclusions: The neuronal conduction pathway between the Vmo and the lateral pterygoid muscle innervates the lateral pterygoid muscle. The neurons are distributed both in the dorsolateral and in the nucleus of the ventral ventricle. It is concluded that the lateral pterygoid muscle involve in the jaw closing and opening movement.


Assuntos
Músculos Pterigoides , Núcleo Motor do Nervo Trigêmeo , Animais , Feminino , Arcada Osseodentária , Movimento , Neurônios , Músculos Pterigoides/anatomia & histologia , Músculos Pterigoides/inervação , Ratos , Ratos Sprague-Dawley , Núcleo Motor do Nervo Trigêmeo/anatomia & histologia , Núcleos do Trigêmeo
17.
J Clin Neurosci ; 76: 205-207, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32291239

RESUMO

Venous malformation (VM) in the posterior cranial fossa occasionally cause trigeminal neuralgia (TN), which were treated with microvascular decompression of its drainer, whereas it was effective only in the limited cases, and its pathological mechanism causing TN is controversial. A 72-year-old man had a 20-year history of typical but severe TN in his left face. Without radiographic evidence of vascular compression on the root entry zone (REZ) of the trigeminal nerve, he underwent stereotactic radiosurgery in previous hospital, resulting in only temporary improvement. On T1-wighted magnetic resonance image with enhancement, the left trigeminal nerve was focally enhanced, which was typical finding after high dose irradiation for TN. Simultaneously, it disclosed small "caput medusa" within the pontine tegmentum, indicated existence of VM in brachium pontis. A 3-dimensional computer graphics model created by fusion of magnetic resonance angiography, diffusion tensor tractography, and fast imaging employing steady-state acquisition elucidated VM was located in the trigeminal nucleus of brachium pontis, which will be very useful for understanding the anatomic correlation of VM and pontine trigeminal nucleus. Since there was no vascular compression at the REZ of the trigeminal nerve, microvascular decompression was not indicated. With minimum dose of gabapentine and carbamazepin, his facial pain completely disappeared and controlled for more than 5 years.


Assuntos
Imageamento Tridimensional , Pedúnculo Cerebelar Médio/diagnóstico por imagem , Nervo Trigêmeo/diagnóstico por imagem , Neuralgia do Trigêmeo/diagnóstico por imagem , Núcleos do Trigêmeo/diagnóstico por imagem , Idoso , Gráficos por Computador , Imagem de Tensor de Difusão , Humanos , Angiografia por Ressonância Magnética , Masculino , Cirurgia de Descompressão Microvascular/efeitos adversos , Pedúnculo Cerebelar Médio/patologia , Radiocirurgia , Nervo Trigêmeo/patologia , Neuralgia do Trigêmeo/patologia , Núcleos do Trigêmeo/patologia
18.
Brain Res ; 1739: 146830, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32278724

RESUMO

An invasive intralaminar thalamic stimulation and a non-invasive application of oral splint are both effective in treating tic symptoms of patients with Tourette syndrome (TS). Therefore, these two treatments may exert some influence on the same brain region in TS patients. We thus hypothesized that the proprioceptive input arising from the muscle spindles of jaw-closing muscles (JCMSs), known to be increased by the application of oral splint, is transmitted to the intralaminar thalamic nuclei. To test this issue, we morphologically and electrophysiologically examined the thalamic projections of proprioceptive input from the JCMSs to the intralaminar thalamic nuclei of rats. We first injected an anterograde tracer, biotinylated dextranamine, into the electrophysiologically identified supratrigeminal nucleus, which is known to receive proprioceptive inputs from the JCMSs via the trigeminal mesencephalic neurons. A moderate number of biotinylated dextranamine-labeled axon terminals were bilaterally distributed in the oval paracentral nucleus (OPC) of the intralaminar thalamic nuclei. We also detected electrophysiological responses to the electrical stimulation of bilateral masseter nerves and to sustained jaw-opening in the OPC. After injection of retrograde tracer (cholera toxin B subunit or Fluorogold) into the OPC, neuronal cell bodies were retrogradely labeled in the rostrodorsal portion of the bilateral supratrigeminal nucleus. Here, we show that proprioceptive inputs from the JCMSs are conveyed to the OPC in the intralaminar nuclei via the supratrigeminal nucleus. This study can help to understand previously unrecognized pathways of proprioception ascending inputs from the brainstem to the thalamus, which may contribute to treatments of TS patients.


Assuntos
Núcleos Intralaminares do Tálamo/fisiologia , Arcada Osseodentária/fisiologia , Propriocepção/fisiologia , Animais , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Tronco Encefálico/fisiologia , Córtex Cerebral/fisiologia , Modelos Animais de Doenças , Arcada Osseodentária/inervação , Masculino , Fusos Musculares/fisiologia , Músculo Esquelético/fisiologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Ratos , Ratos Wistar , Núcleos Talâmicos , Síndrome de Tourette/fisiopatologia , Núcleos do Trigêmeo
19.
Neuropharmacology ; 170: 108029, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32278976

RESUMO

Migraine is an extraordinarily prevalent and disabling headache disorder that affects one billion people worldwide. Throbbing pain is one of several migraine symptoms including sensitivity to light (photophobia), sometimes to sounds, smell and touch. The basic mechanisms underlying migraine remain inadequately understood, and current treatments (with triptans being the primary standard of care) are not well tolerated by some patients. NOP (Nociceptin OPioid) receptors, the fourth member of the opioid receptor family, are expressed in the brain and periphery with particularly high expression known to be in trigeminal ganglia (TG). The aim of our study was to further explore the involvement of the NOP receptor system in migraine. To this end, we used immunohistochemistry to examine NOP receptor distribution in TG and trigeminal nucleus caudalus (TNC) in mice, including colocalization with specific cellular markers, and used nitroglycerin (NTG) models of migraine to assess the influence of the selective NOP receptor agonist, Ro 64-6198, on NTG-induced pain (sensitivity of paw and head using von Frey filaments) and photophobia in mice. Our immunohistochemical studies with NOP-eGFP knock-in mice indicate that NOP receptors are on the majority of neurons in the TG and are also very highly expressed in the TNC. In addition, Ro 64-6198 can dose dependently block NTG-induced paw and head allodynia, an effect that is blocked by the NOP antagonist, SB-612111. Moreover, Ro 64-6198, can decrease NTG-induced light sensitivity in mice. These results suggest that NOP receptor agonists should be futher explored as treatment for migraine symptoms. This article is part of the special issue on Neuropeptides.


Assuntos
Imidazóis/uso terapêutico , Transtornos de Enxaqueca/induzido quimicamente , Transtornos de Enxaqueca/tratamento farmacológico , Nitroglicerina/toxicidade , Receptores Opioides/agonistas , Compostos de Espiro/uso terapêutico , Núcleos do Trigêmeo/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Feminino , Imidazóis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transtornos de Enxaqueca/metabolismo , Receptores Opioides/metabolismo , Compostos de Espiro/farmacologia , Núcleos do Trigêmeo/metabolismo
20.
Int J Mol Sci ; 21(7)2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32283868

RESUMO

Irreversible pulpitis is an extremely painful condition and its consequence in the central nervous system (CNS) remains unclear. A mouse model of dental pulp injury (DPI) resembles the irreversible pulpitis profile in humans. This study sought to determine whether pain induced by DPI activates microglia and astrocytes in the trigeminal subnucleus caudalis (Vc), as well as increases levels of proinflammatory cytokines, and whether electroacupuncture (EA) can be a potential analgesic and neuroprotective therapy following DPI. Pain behavior was measured via head-withdrawal threshold (HWT) and burrowing behavior at days 1, 3, 7, 14 and 21 after DPI. A marked decrease in HWT and burrowing activity was observed from day 1 to 14 after DPI and no changes were seen on day 21. Microglial and astrocytes activation; along with high cytokine (TNFα, IL-1ß, and IL-6) levels, were observed in the Vc at 21 days after DPI. These effects were attenuated by verum (local and distal) EA, as well as oral ibuprofen administration. The results suggest that DPI-induced pain and glial activations in the Vc and EA exert analgesic efficacy at both local and distal acupoints. Furthermore, verum (local and distal) EA might be associated with the modulations of microglial and astrocytes activation.


Assuntos
Analgésicos/farmacologia , Polpa Dentária/efeitos dos fármacos , Polpa Dentária/lesões , Eletroacupuntura , Fármacos Neuroprotetores/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Comportamento Animal , Citocinas/genética , Citocinas/metabolismo , Polpa Dentária/metabolismo , Polpa Dentária/patologia , Modelos Animais de Doenças , Eletroacupuntura/métodos , Expressão Gênica , Histocitoquímica , Mediadores da Inflamação/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Pulpite/tratamento farmacológico , Pulpite/etiologia , Pulpite/metabolismo , Pulpite/patologia , Ratos , Núcleos do Trigêmeo/citologia , Núcleos do Trigêmeo/efeitos dos fármacos , Núcleos do Trigêmeo/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...