• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.365-374
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• 2021

The mammalian target of rapamycin (mTOR) plays a role in various cellular phenomena, including autophagy, cell proliferation, and differentiation. Although recent studies have reported its involvement in nociceptive responses in several pain models, whether mTOR is involved in orofacial pain processing is currently unexplored. This study determined whether rapamycin, an mTOR inhibitor, reduces nociceptive responses and the number of Fos-immunoreactive (Fos-ir) cells in the trigeminal nucleus caudalis (TNC) in a mouse orofacial formalin model. We also examined whether the glial cell expression and phosphorylated p38 (p-p38) mitogen-activated protein kinases (MAPKs) in the TNC are affected by rapamycin. Mice were intraperitoneally given rapamycin (0.1, 0.3, or 1.0 mg/kg); then, 30 min after, 5% formalin (10 μl) was subcutaneously injected into the right upper lip. The rubbing responses with the ipsilateral forepaw or hindpaw were counted for 45 min. High-dose rapamycin (1.0 mg/kg) produced significant antinociceptive effects in both the first and second phases of formalin test. The number of Fos-ir cells in the ipsilateral TNC was also reduced by high-dose rapamycin compared with vehicle-treated animals. Furthermore, the number of p-p38-ir cells the in ipsilateral TNC was significantly decreased in animals treated with high-dose rapamycin; p-p38 expression was co-localized in microglia, but not neurons and astrocytes. Therefore, the mTOR inhibitor, rapamycin, reduces orofacial nociception and Fos expression in the TNC, and its antinociceptive action on orofacial pain may be associated with the inhibition of p-p38 MAPK in the microglia.

• Journal of Electrodiagnosis and Neuromuscular Diseases
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• v.20 no.2
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• pp.144-147
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• 2018

Although dysgeusia can occur as a consequence of stroke attacks, many physicians and patients tend to overlook it. A 50-year old woman complained of a 2-week history of abnormal sense of taste on the anterior two-thirds of right tongue. Blink reflex test demonstrated prolonged ipsilateral and contralateral R2 responses with the right supraorbital nerve stimulations, which suggest the lesion on the descending pathway. Brainstem magnetic resonance imaging (MRI) demonstrated abnormal findings in the right lower dorsal pons, anterior to 4th ventricle, lateral to inferior colliculus, and at the level of the pontomedullary junction, which was compatible with solitary tract nucleus and spinal trigeminal nucleus. Brainstem infarction should be considered in patients who have abnormal sense of taste. Additionally, blink reflex test may be helpful for the detection of central origin dysgeusia.

• Journal of Korean Neurosurgical Society
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• v.29 no.8
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• pp.985-994
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• 2000

Objective : There are some advantages of trigeminal evoked potential(TEP) recording compared to other somatosensory evoked potential(SSEP) recordings. The trigeminal sensory pathway has a pure sensory nerve branch, a broader receptive field in cerebral cortex, and a shorter pathway. Despite these advantages, there is little agreement as to what constitutes a normal response and what wave forms truly characterize the intraoperative TEP. This study presents the normative data of TEP recorded on the epidural surface of the rat with a platinum ball electrode. Materials & Methods : Under general anesthesia with urethane, the adult Sprague-Dawley male rats(300-350g) were given electrical stimulation with two stainless steel electrodes which were inserted into the subcutaneous layer of the area around whiskers. A reference electrode was positioned in the temporalis muscle ipsilateral to the recording site. Results : TEPs were recorded in the Par I area of somatosensory cortex and recorded most apparently on the point of 2mm posterior from the bregma and 6mm lateral from the midline. The typical wave form consisted of 5 peaks (N1-P1-N2-P2-N3 according to emerging order, upward negativity). Each latency to corresponding peaks was not influenced by the different intensities of stimulation, especially from 1 to 5mA. Average latencies of 5 peaks were in the following order ; 7.7, 11.1, 15, 22.3, 29.4ms. There was also no significant difference between latencies before and after administration of muscle relaxant(pancuronium). For the electrophysiological localization of recorded waves, the action potential of a single unit was recorded with glass microelectrode(filled with 2M NaCl, $3-5M{\Omega}$) in the thalamus of rat. A sharp wave was recorded in the VPM nucleus, in which the latency was shorter than that of N1. This suggests that all 5 peaks were generated by neural activities in the suprathalamic pathway. Conclusion : In terms of recording near-field potentials, our data also suggests that TEP in the rat may be superior to other SSEPs. In overall, these results may afford normative data for the studies of supratentorial lesions such as hydrocephalus or cerebral ischemia which can have an influence on near-field potentials.

• Restorative Dentistry and Endodontics
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• v.27 no.6
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• pp.587-599
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• 2002

Extracellular single unit recordings were made from the ventral posteromedial thalamic (VPM) nociceptive neurons to determine mechanoreceptive field (RF) and response properties. A total of 44 VPM thalamic nociceptive neurons were isolated from rats anesthetized with urethane-chloralose. Based on responses to various mechanical stimuli including touch, pressure and pinch applied to the RF, 32 of 44 neurons were classified as nociceptive specific (NS) neuron. The other 12 neurons, classified as wide dynamic range (WDR), showed a graded response to increasingly intense stimuli, with a maximum discharge to noxious pinch. The VPM nociceptive neurons showed various spontaneous activity ranged from 0-6 Hz. They were located throughout the VPM, and had an contralateral RF including mainly intraoral (and perioral) regions. The RF size was relatively small, and very few neurons had a receptive field involving 3 trigeminal divisions. The NS neurons activated only by pressure and pinch stimuli had high mechanical thresholds compared to WDR neurons activated also by touch stimuli. The VPM nociceptive neurons were tested with suprathershold graded mechanical stimuli. Most of 21 NS and 8 WDR neurons showed a progressive increase in number of spikes as mechanical stimulus intensity was increased. In some neurons, the responses reached a peak before the highest intensity was given. Application of 5 mM $CoCl_2{\;}(10{\;}{\mu}\ell)$ solution to the trigeminal subnucleus caudalis did not produce any significant changes in the spontaneous activity, RF size, mechanical threshold, and response to suprathreshold mechanical stimuli of 9 VPM nociceptive neurons tested. 17 of 33 VPM nociceptive neurons responded to noxious heat as well as noxious mechanical stimuli applied to their RF. Application of the mustard oil, a small-fiber excitant and inflammatory irritant, to the right maxillary first molar tooth pulp induced an immediate but short-lasting neuronal discharges upto approximately 4 min in 16 of 42 VPM nociceptive neurons. These results suggest that VPM thalamic nucleus may contribute to the sensory discriminative aspect of orofacial nociception.

• Restorative Dentistry and Endodontics
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• v.24 no.4
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• pp.614-622
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• 1999

Recent studies have implicated that more rostral components of the trigeminal spinal nucleus including subnucleus oralis (Vo) in orofacial nociceptive mechanisms. Since there is only limited electrophysiological evidence, the present study was initiated to characterize the receptive field and response properties of malls nociceptive neurons in chloralose/urethan-anesthetized rats. Single neuronal activity was recorded in right subnucleus oralis, and types of nociceptive neurons classified wide dynamic range (WDR), NS (nociceptive specific) and deep nociceptive (D) and the mechanoreceptive field (RF) and response properties were determined. A total of 34 nociceptive neurons could be subdivided into 17WDR neurons, 12NS neurons and 5D neurons. Vo nociceptive neurons had RF involving maxillary and/or mandibular divisions mainly located in the intraoral and/or perioral regions. Majority of Vo nociceptive neurons showed spontaneous activity less than 1Hz. The NS and D neurons activated only by heavy pressure and/or pinch stimuli had high mechanical thresholds compared to WDR neurons activated also by tactile stimuli. Vo nociceptive neurons showed a progressive increase of response to the graded mechanical stimuli. 39% of Vo nociceptive neurons received C-fiber electrical input as well as A-fiber electrical input from their RF, and 45% of them responded to electrical stimulation of the right maxillary first molar. 41% of Vo nociceptive neurons responded to noxious heat applied to their RF, and 18% of them showed an immediate burst of discharges following MO application to the right maxillary first molar pulp. These results indicate that Vo is involved in the transmission of nociceptive information mainly coming from intraoral or perioral region including tooth pulp.

• Korean Journal of Veterinary Research
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• v.36 no.4
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• pp.859-871
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• 1996

This study was conducted to elucidate the distribution of Aujeszky's disease viral nucleic acids and antigens in the central nervous system (CNS) of piglets. The first Korean isolate of Aujeszky's disease virus(ADV) that isolated from naturally infected piglets in Yang San, was inoculated into 32 day old piglets with $10^{5.9}TCID_{50}/ml$ through intranasal or intramuscular route. These piglets were sacrificed at every 24hrs for 8 days. The immunohistochemistry (IHC) was conducted to detect the viral antigens in paraffin-embedded tissue sections using avidin-biotin-peroxidase complex (ABC) method. The viral nucleic acids were detected by in situ hybridization (ISH) using ADV specific DNA probe labeled with digoxigenin. The ADV antigens were detected in reticuloendothelial cells of spleen, lymph nodes and tonsil, alveolar walls, leptomeningeal vascular walls, inflammatory foci of each organ, and nerve cells. The viral nucleic acids were detected in the spinal trigeminal nucleus and its tracts of the pons and medulla oblongata by the ISH technique. The pathways of AD viruses in CNS were determined by IHC and ISH. In the intranasally inoculated group, the viruses in nasal mucosa moved to medulla oblongata and pons through the trigeminal nerve. In case of intramuscullarly inoculated group, viruses moved to brain via lymphoid organs or spinal nerves from sciatic nerves.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.16 no.3
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• pp.321-347
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• 1994

Muscle spindle afferents from masseter muscle were labelled by the intra-axonal HRP injection and were processed for light microscopic reconstruction. Regions containing terminal arbors scattered in the central portion of the masseteric motor neuron pool (type I a) and those restricted to 2-3 small portion of it (type II) were selected and processed for electronmicroscopic analysis with serial sections. The shape of the labelled boutons was dome or elongated shape. Scalloped or glomerulus shape with peripherial indentation containing pre or postsynaptic neuronal propiles, which is occasionally found in the trigeminal main sensory nucleus and spinal dorsal horn, was not observed. Both type Ia and type II boutons had pale axoplasm and contained clear, spherical vesicles of uniform size(dia : 49-52nm) and occasionally large dense cored vesicles(dia : 87-118nm). The synaptic vesicles were evenly distributed throughout the boutons although there was a slight tendency of vesicles to accumulate at the presynaptic site. The average of short and long diameter(short D. + long D./2) of type I a bouton was smaller than that of type II bouton. All the labelled boutons, which showed prominent postsynaptic density, large synaptic area and multiple synaptic contact, made asymmetrical synaptic contact with postsynaptic neuronal propiles. Most of the type Ia and type II boutons made synaptic contact with only one neuronal propile and boutons which shows synaptic contact or more neuronal propiles was not observed. Most of the type Ia boutons(87.2%) were presynaptic to the soma or proximal dendrite and a few remainder(12.8%) made synaptic contact with dendritic shaft or distal dendrite. In contrast, majority of type II boutons showed synaptic contact with dendritic shaft and remainder with soma or proximal dendrite. In conclusion, terminal boutons which participate in the excitatory monosynaptic jaw jerk reflex made synaptic contact with more proximal region of the neuron, and showed very simple synaptic connection, compared with those from the primary afferenst in the other region of the central nervous system such as spinal dorsal horn and trigeminal main sensory nucleus which assumed to be responsible for the mediating pain, tactile sensation, sensory processing or sensory discrimination.

• Applied Microscopy
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• v.42 no.1
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• pp.9-16
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• 2012

The goal of this study was to identify neurotransmitters in endings (p-endings) presynaptic to low-threshold mechanoreceptive vibrissa afferents in the laminae III/IV of cat trigeminal caudal nucleus (Vc). Rapidly-adapting vibrissa afferents were intra-axonally labeled after electrophysiological identification, and postembedding immunogold staining with antisera against ${\gamma}$-aminobutyric acid (GABA) and glycine was performed, followed by quantitative ultrastructural analysis of p-endings presynaptic to the labeled vibrissa afferent terminals. Sixteen p-endings, which are presynaptic to the HRP-labeled vibrissa afferent terminals, were analyzed in this study: Eight p-endings (50%, 8/16) were immunopositive to GABA but immunonegative to glycine (GABA+ p-ending), and remaining 8 p-endings (50%, 8/16) exhibited immunoreactivity to both GABA and glycine. Bouton volume of the p-endings was not significantly different between the two groups. However, the p-endings differed from each other in relative content of GABA and glycine. These findings suggest that low-threshold mechanoreceptive information conveyed through vibrissa afferent at Vc is presynaptically modulated by GABA and/or glycine, and that degree of presynaptic modulation may differ among each vibrissa afferent terminal.

• Applied Microscopy
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• v.38 no.3
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• pp.151-157
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• 2008

Trigeminal primary afferents expressing $P2X_3$ or transient receptor potential vanilloid 1 (TRPV1) are involved in the transmission of nociceptive information. In order to characterize $P2X_3$- and TRPV1-immunopositive neurons in the trigeminal ganglion (TG) and trigeminal caudal nucleus (Vc), we performed immunofluorescence experiments using anti-$P2X_3$ and anti-TRPV1 antisera and a morphometric analysis. 77.4% (1,401/1.801) of all the $P2X_3$-postive neurons coexpressed TRPV1 and 51.9% (1,401/2,698) of all the THFV1-immunopositive neurons also costained for $P2X_3$ in the TG. Immunoreactivity for both $P2X_3$ and TRPV1 were present in medium-sized neurons but not in small- and large-sized neurons. $P2X_3$ and/or TRPV1-immunopositive fibers were observed in the primary afferents and their associated axons in the Vc. These fibers and terminals were distributed in the superficial lamina of Vc: $P2X_3$-immunopositive fibers and terminals were distributed in the lamina I and II, expecially in the inner part of lamina II (lamina IIi), whereas TRPV1-immunopositive ones were densely detected in the lamina I and outer part of lamina II (lamina IIo). Immunopositive fibers and terminals for both $P2X_3$ and TRPV1 were observed on the border between lamina IIi and IIo. These results suggest that terminals coexpressing $P2X_3$ and TRPV1 are involved in specific roles in the transmission and processing of orofacial nociceptive information.

• The Korean Journal of Physiology
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• v.25 no.1
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• pp.87-99
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• 1991

In order to elucidate whether capsaicin applied topically acts as a pain-producing subastance or as a tastant, neuronal activities of the chorda tympani nerve(CN), lingual nerve(LN), solitary tract nucleus(STN), and trigeminal nucleus(TGN) were recorded while thermal and taste stimuli, and capsaicin were being applied topically, and algesics intra-arterially to the tongue of cats anesthetized with ${\alpha}-chloralsoe$. In addition, the STN neurons were examined after wheat germ agglutinin-horseradish peroxidase(WGA-HRP) was applied to the CN. The CN fibers responded to taste and thermal stimuli, algesics, and capsaicin. Responses to capsaicin were significantly correlated with those to taste and thermal stimuli. The LN fibers mainly responded to mechanical and thermal stimuli, algesics, and capsaicin. Responses to capsaicin were significantly correlated with those to algesics. The STN neurons responded to taste and thermal stiumli, algesics, and capsaicin. Responses to capsaicin were significantly correlated with those to taste and thermal stiumli in somewhat different fashion from those of the CN fibers. The TGN neurons mainly responded to mechanical stimuli, algesics, and capsaicin. Correlations between responses to capsaicin and any others were not significant. After WGA-HRP was applied to the CN, the STN neurons which receive input from the CN were identified largely in the medio-ventral portion to the solitary tract. These results suggest that capsaicin produce taste as well as pain sensation. Sensory information evoked by capsaicin can be conveyed to the STN, especially medio-ventral portion, via the CN as gustatory information on the one hand, and to the STN or TGN via the LN as noxious information on the other. In addiation, the noxious information may be conveyed to the STN via the CN.