• The Korean Journal of Pain
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• v.13 no.2
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• pp.143-148
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• 2000

Background: Trigeminovascular system is implicated in the pathophysiology of the headache in migraine. This study was designed to evaluate the pattern of Fos protein expression in trigeminal nociceptive central pathway after meningeal stimulation of rats by capsaicin. Methods: The expression of Fos protein was examined by immunohistochemistry in thalamus, brainstem and upper cervical cord (at three levels corresponding to obex, 0.8 mm and 2 mm below obex) 2 hours after intracisternal injection of either diluted capsaicin solution (0.1 ml, $61{\mu}g/ml$) or normal saline (0.1 ml) through a catheter placed in the cisterna magna, or following epidural instillation of diluted capsaicin solution in urethane-anesthetized Sprague-Dawley rats. Results: Fos immunoreactivity was strongly expressed within lamina I, II of bilateral trigeminal nucleus caudalis (TNC) after cisternal capsaicin injection and magnitude of expression was greatest at level 2.0 mm below obex. Epidural capsaicin caused much less labelling than cisternal capsaicin. Fos positive cells were also observed in area postrema, nucleus of the solitary tract, medullary reticular nucleus and midline nuclear groups of the thalamus with similar intensity between capsaicin and control group. Conclusions: These results indicate that the injection of capsaicin into the cisterna magna is an effective stimulus for the induction of Fos protein within TNC through activation of trigeminovascular afferents and this animal model can be useful for the evaluation of the pathophysiology and drug development in migraine and related headache.

• Journal of Dental Anesthesia and Pain Medicine
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• v.19 no.2
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• pp.77-82
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• 2019

It is well known that trigeminal nerve injury causes hyperexcitability in trigeminal ganglion neurons, which become sensitized. Long after trigeminal nerve damage, trigeminal spinal subnucleus caudalis and upper cervical spinal cord (C1/C2) nociceptive neurons become hyperactive and are sensitized, resulting in persistent orofacial pain. Communication between neurons and non-neuronal cells is believed to be involved in these mechanisms. In this article, the authors highlight several lines of evidence that neuron-glial cell and neuron macrophage communication have essential roles in persistent orofacial pain mechanisms associated with trigeminal nerve injury and/or orofacial inflammation.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.121-125
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• 2013

The purpose of this study is to investigate the antinociceptive effects of ginsenosides on toothache. c-Fos immunoreactive (IR) neurons were examined after noxious intrapulpal stimulation (NS) by intrapulpal injection of 2 M KCl into upper and lower incisor pulps exposed by bone cutter in Sprague Dawley rats. The number of Fos-IR neurons was increased in the trigeminal subnucleus caudalis (Vc) and the transitional region between Vc and subnucleus interpolaris (Vi) by NS to tooth. The intradental NS raised arterial blood pressure (BP) and heart rate (HR). The number of Fos-IR neurons was also enhanced in thalamic ventral posteromedial nucleus (VPMN) and centrolateral nucleus (CLN) by NS to tooth. The intradental NS increased the number of Fos-IR neurons in the nucleus tractus solitarius (NTS) and rostral ventrolateral medulla (RVLM), hypothalamic supraoptic nucleus (SON) and paraventricular nucleus (PVN), central cardiovascular regulation centers. Ginsenosides reduced the number of c-Fos-IR increased by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Naloxone, an opioid antagonist, did not block the effect of ginsenoside on the number of Fos-IR neurons enhanced by NS to tooth in the trigeminal Vc and thalamic VPMN and CLN. Ginsenosides ameliorated arterial BP and HR raised by NS to tooth and reduced the number of Fos-IR neurons increased by NS to tooth in the NTS, RVLM, hypothalamic SON, and PVN. These results suggest that ginsenosides have an antinociceptive effect on toothache through non-opioid system and attenuates BP and HR increased by NS to tooth.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.5
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• pp.379-383
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• 2009

Nitric oxide (NO), a diffusible gas, is produced in the central nervous system, including the spinal cord dorsal horn and the trigeminal nucleus, the first central areas processing nociceptive information from periphery. In the spinal cord, it has been demonstrated that NO acts as pronociceptive or antinociceptive mediators, apparently in a concentration-dependent manner. However, the central role of NO in the trigeminal nucleus remains uncertain in support of processing the orofacial nociception. Thus, we here investigated the central role of NO in formalin (3%)-induced orofacial pain in rats by administering membrane-permeable or -impermeable inhibitors, relating to the NO signaling pathways, into intracisternal space. The intracisternal pretreatments with the NO synthase inhibitor L-NAME, the NO-sensitive guanylate cyclase inhibitor ODQ, and the protein kinase C inhibitor GF109203X, all of which are permeable to the cell membrane, significantly reduced the formalin-induced pain, whereas the membrane-impermeable NO scavenger PTIO significantly enhanced it, compared to vehicle controls. These data suggest that an overall effect of NO production in the trigeminal nucleus is pronociceptive, but NO extracellularly diffused out of its producing neurons would have an antinociceptive action.

• Korean Journal of Veterinary Research
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• v.34 no.3
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• pp.583-591
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• 1994

This study was carried out to investigate the pathogenesis of canine herpesvirus(CHV) infection in dogs. The 17 puppies, one day old, delivered from CHV seronegative 3 dams were divided into two groups. The 13 puppies were inoculated intranasally with 1ml of CHV-KK inoculum($5{\times}10^{5.6}TCID_{50}/ml$) and 4 puppies were served as control. And then the puppies were sacrificed at 2, 4, 6 and 7 days after the treatment, and sampled nasal mucosa, trigeminal nerve, trigeminal ganglion, bone marrow, eye, brain and other major organs for the immunohistochemical examination. Distribution of CHV antigens was limited in cytoplasms and nuclei of necrotic nasal epthelia at 2 days after infection. At 4 days after infection, CHV antigens were detected in vascular walls and peripheral nerves of nasal lamina propria, reticuloendothelial cells of spleen, interstitium of kidney, leptomeningeal vascular walls and alveolar walls, At 6 and 7 days after infection, CHV antigens were detected in all of the necrotic area. CHV antigens were also detected in vascular endothelial cells of various organs and in blood leukocytes from 4 days after infection. Among the six puppies in which necrotic lesions of central nervous system were observed, CHV antigens were detected in trigeminal ganglion, trigeminal nerve and ventroposteriomedial nucleus of four puppies and in spinal trigeminal nucleus of three puppies. These results indicate that the generalized focal necrosis of all organs including brain and eyes in canine herpesvirus infection were resulted from generalized vasculitis with leukocyte-associated viremia, and also the hemonecrotizing meningoencephalitis was resulted from spreading of CHV via blood and nerve trunk.

• Korean Journal of Acupuncture
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• v.17 no.1
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• pp.101-121
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• 2000

The purpose of this morphological studies was to investigate the relation to the meridian, acupoint and nerve. The common locations of the spinal cord and brain projecting to the the gallbladder, GB34 and common peroneal nerve were observed following injection of transsynaptic neurotropic virus, pseudorabies virus(PRV), into the gallbladder, GB34 and common peroneal nerve of the rabbit. After survival times of 96 hours following injection of PRV, the thirty rabbits were perfused, and their spinal cord and brain were frozen sectioned($30{\mu}m$). These sections were stained by PRV immunohistochemical staining method, and observed with light microscope. The results were as follows: 1. In spinal cord, PRV labeled neurons projecting to the gallbladder, GB34 and common peroneal nerve were founded in thoracic, lumbar and sacral spinal segments. Densely labeled areas of each spinal cord segment were founded in lamina V, VII, X, intermediolateral nucleus and dorsal nucleus. 2. In medulla oblongata, The PRV labeled neurons projecting to the gallbladder, GB34 and common peroneal nerve were founded in the A1 noradrenalin cells/C1 adrenalin cells/caudoventrolateral reticular nucleus, rostroventrolateral reticular nucleus, medullary reticular nucleus, dorsal motor nucleus of vagus nerve, nucleus tractus solitarius, raphe obscurus nucleus, raphe pallidus nucleus, raphe magnus nucleus, gigantocellular nucleus, lateral paragigantocellular nucleus, principal sensory trigeminal nucleus and spinal trigeminal nucleus. 3. In Pons, PRV labeled neurons were parabrachial nucleus, Kolliker-Fuse nucleus and cochlear nucleus. 4. In midbrain, PRV labeled neurons were founded in central gray matter and substantia nigra. 5. In diencephalon, PRV labeled neurons were founded in lateral hypothalamic nucleus, suprachiasmatic nucleus and paraventricular hypothalamic nucleus. 6. In cerebral cortex, PRV labeled neuron were founded in hind limb area.This results suggest that PRV labeled common areas of the spinal cord projecting to the gallbladder, GB34 and common peroneal nerve may be first-order neurons related to the somatic sensory, viscero-somatic sensory and symapathetic preganglionic neurons, and PRV labeled common area of the brain may be first, second and third-order neurons response to the movement of smooth muscle in gallbladder and blood vessels.These PRV labeled neurons may be central autonomic center related to the integration and modulation of reflex control linked to the sensory system monitoring the internal environment, including both visceral sensation and various chemical and physical qualities of the bloodstream. The present morphological results provide that gallbladder meridian and acupoint may be related to the central autonomic pathways.

• International Journal of Oral Biology
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• v.30 no.2
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• pp.71-76
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• 2005

The mesencephalic trigeminal nucleus (Mes V) contains cell bodies of primary afferent sensory neurons that relay proprioceptive information from the periodontium and masticatory muscles and function as typical sensory neurons or potentially as integrative interneurons. In the present study, we studied these two potential functions using combined experimental approaches of retrograde labeling and whole cell patch clamp recording. Mes V neurons that presumably originate from periodontal nerve fibers in subsets of Mes V nucleus were identified by retrograde labeling with a fluorescent dye, DiI, which was applied onto inferior alveolar nerve. These cells were elliptical perikarya shaped cells about $40{\mu}m$ in diameter. In these neurons, we measured high voltage-activated calcium channel (HVACC) currents. $GABA_B$ agonist, baclofen, inhibited calcium currents, and the HVACC currents inhibition by baclofen was voltage-dependent, exhibited prepulse facilitation, indicating that it was mediated by $G_i/_G_o$ protein. Taken together, our results demonstrate that Mes V neurons not only have cell bodies originating from periodontium, but also receive synaptic inputs including GABAergic neurons suggesting that Mes V neurons function as both primary sensory neurons and integrative interneurons.

• Applied Microscopy
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• v.28 no.3
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• pp.255-262
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• 1998

This study was performed to observe the morphological changes of the synaptic structures in the interpolar part of the spinal trigeminal nucleus of rat during aging. Transmission electron microscopy has been used to determine the r)umber of synapses, length of postsynaptic densities, number and area of axon terminals. Sprague-Dawley rat 3, 12, 24 and 36 months of age were used in this study. 1. The number of synapses was 51.7, 43.1, 28.4 and 16.8 in the 3, 12, 24 and 36 months of age respectively. Therefore, the number of synapses decreased gradually with age, but decreased significantly in the 24 and 36 months. 2. The length of postsynaptic densities was $30.2{\mu}m,\;23.6{\mu}m,\;10.4{\mu}m\;and\;4.9{\mu}m$ in the 3, 12, 24 and 36 months of age respectively. Therefore, the length of postsynaptic densities decreased gradually with age, but decreased significantly in the 24 and 36months. 3. The number of axon terminals was 84.3, 73.7, 51.4 and 26.6 in the 3, 12, 24 and 36 months of age respectively. Therefore, the number of axon terminals decreased gradually with age, but decreased significantly in the 24 and 36months. 4. The area of axon terminals was $76.1{\mu}m^2,\;64.1{\mu}m^2,\;29.9{\mu}m^2\;and\;13.8{\mu}m^2$ in the 3, 12, 24 and 36 months of age respectively. Therefore, the area of axon terminals decreased gradilally with age, but decreased significantly in the 24 and 36 months. The results suggest that there are the changes of the synaptic structures in the interpolar part of spinal trigeminal nucleus of rat during aging. These changes nay be concerned to the decreased function of mediating pain and temperature sensation in the face and oral cavity during aging.

• Korean Journal of Veterinary Research
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• v.34 no.3
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• pp.569-581
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• 1994

This study was carried out to investigate the pathogenesis of canine herpesvirus(CHV) infection in dogs. The 17 puppies, one day old, delivered from CHV seronegative 3 dams were divided into two groups. The 13 puppies were inoculated intranasally with 1ml of CHV-KK inoculum($5{\times}10^{5.6}TCID_{50}/ml$) and 4 puppies were served as control. And then the puppies were sacrificed at 2, 4, 6 and 7 days after the treatment, and collected blood, nasal mucosa, trigeminal nerve, trigeminal ganglion, bone marrow, eye, brain and other major organs. These organs were examined histopathologically and electron microscopically. The platelets of puppies infected with CHV were dramatically decreased because of the damages of vascular endothelial cells. Histopathologically, necrotizing vasculitis and neuritis were proceeded the generalized focal necrosis of all organs. Necrotic changes in trigeminal ganglion, trigeminal nerve and ventroposteriomedial nucleus of thalamus were observed in 4 puppies infected with CHV. Herpesviral particles, various forms of maturation, were observed in endothelial cells of the alveolar capillary and hepatic sinusoid with electron microscopy. These results suggest that the generalized focal necrcsis of all organs including brain and eyes in canine herpesvirus infection were resulted from generalized vasculitis, and also the hemonecrotizing meningoencephalitis was related to the necrosis of trigeminal nerve pathway.

• Journal of Oral Medicine and Pain
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• v.30 no.1
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• pp.87-106
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• 2005

In order to evaluate the mechanism of transmission as well as processing of sensory information originating from low-threshold mechanoreceptor in oral and maxillofacial region at primary synaptic region of trigeminal nervous system, vibrissa afferent fibers of adult cat were labeled with intra-axonal HRP injection. Serial sections containing labeled boutons were obtained from the piece of trigeminal interpolar nucleus. Under electron microscope, total 30 labeled boutons were observed, and ultrastructural characteristics, frequency of occurence, synaptic organizations of vibrissa afferent terminals were analysed. The results were as follows: 1. Labeled boutons contained clear, spherical synaptic vesicles with diameter of 45$\sim$55nm. They formed asymmetrical synapse with dendrites showing definite postsynaptic density, larger synaptic cleft, multiple synaptic structures at various regions. With unlabeled axon terminals(p-ending) containing polymorphic synaptic vesicles, they formed symmetrical synapse showing indefinite postsynaptic density and narrower synaptic area. 2. Each labeled bouton formed 1 to 15 synapses, the average of 4.77$\pm$3.37 contacts per labeled bouton, with adjacent neuronal profiles. Relatively complex synaptic organization, which formed synapses with more than 5 neuronal profiles, was observed in a large number(46.7%, n=14) of labeled boutons. 3. Axo-somatic synapse was not observed. The number of axo-dendritic synapse was 1.83$\pm$1.37 per labeled bouton. Majority(85.0%) of axo-dendritic synapses were formed with dendritic shafts, nonprimary dendrites(n=47, 1.57$\pm$1.38/1 bouton), however, synapses formed with primary dendrites(n=6, 0.20$\pm$0.41/1 bouton) or dendritic spines(n=2, 0.07$\pm$0.25/1 bouton) were rare. 4. 76.7%(n=23) of labeled boutons formed axo-axonic synapse (2.93$\pm$2.36/1 bouton) with p-endings containing pleomorphic vesicles. Synaptic triad, in which p-endings formed synapses with labeled boutons and dendrites adjacent to the labeled boutons simultaneoulsy, were also observed in 60.0%(n=18) of labeled boutons. From the above results, vibrissa afferent terminals of adult cat showed distinctive synaptic organization in the trigeminal interpolar nucleus, thus, suggests their correlation with the function of the trigeminal interpolaris nucleus, which participates in processing of complex sensory information such as two-point discrimination and motivational-affective action. Further studies on physiologic functions such as quantitative analysis on ultrastructures of afferent terminals and nerve transmitters participating in presynaptic inhibition are required.