• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.425-429
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• 2009

Intracranial headaches, including migraines, are mediated by nociceptive activation of the trigeminal nucleus caudalis (TNC), but the precise mechanisms are poorly understood. We previously demonstrated that selective blockage of spinal sigma-1 receptors (Sig-1R) produces a prominent antinociceptive effect in several types of pain models. This study evaluates whether the Sig-1R antagonist (BD1047) has an antinociceptive effect on capsaicin (a potent C-fiber activator) induced headache models in rats. Intracisternal infusion of capsaicin evoked pain behavior (face grooming), which was significantly attenuated by BD1047 pretreatment. BD1047 consistently reduced capsaicin-induced Fos-like immunoreactivity (Fos-LI), a neuronal activator, in the TNC in a dose-dependent manner. Moreover, capsaicininduced phosphorylation of N-methyl-D-aspartate receptor subunit 1 was reversed by BD1047 pretreatment in the TNC. These results indicate that the Sig-1R antagonist has an inhibitory effect on nociceptive activation of the TNC in the capsaicin-induced headache animal model.

• The Korean Journal of Pain
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• v.31 no.3
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• pp.174-182
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• 2018

Background: The trigeminal nucleus caudalis (Vc) is a primary central site for trigeminal transmitting. Noxious stimulation of the trigeminal nociceptors alters the central synaptic releases and neural expression of some inflammatory and trophic agents. Orexin-A and the orexin 1 receptor (OX1R) are expressed in pain pathways including trigeminal pain transmission. However, the the mechanism(s) underling orexin-A effects on trigeminal pain modulation have not been fully clarified. Methods: Trigeminal pain was induced by subcutaneous injection of capsaicin in the upper lip in rats. The effect of trigeminal pain on cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) expression in the Vc of animals was determined by immunofluorescence. Subsequently, OX1R agonist (orexin-A) and antagonist (SB-334867-A) was administrated in the Vc to investigate the possible roles of the Vc OX1R on changes in COX-2 and BDNF levels following pain induction. Results: The data indicated an increase in COX-2 and decrease in BDNF immuno-reactivity in the Vc of capsaicin, and capsaicin- pretreated with SB-334867-A (80 nM), groups of rat. However, the effect of capsaicin on COX-2 and BDNF expressions was reversed by a Vc microinjection of orexin-A (100 pM). Conclusions: Overall, the present data reveals that orexin-A can attenuate capsaicin-induced trigeminal pain through the modulation of pain effects on COX-2 and BDNF expressions in the Vc of rats.

• Proceedings of the Korean Society for Emotion and Sensibility Conference
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• 2002.11a
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• pp.140-147
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• 2002

시상은 체감각 정보를 처리하는데 있어서 매우 중요한 역할을 하는 부위이다. 본 연구는 운동장애 환자의 시상에서 뉴론의 활동 특성을 알아보기 위해 수행되었다. 그 결과 체감각으로서의 운동자극에 반응하는 뉴론이 essential tremor (ET) 환자의 nucleus ventralis intermedius (VIM)에서 발견되었다. ET 환자 뉴론의 평균 활동율(firing rate)은 Parkinson's disease (PD) 환자 보다 높았다. 또한 ET 환자의 VIM에서 운동자극에 반응하는 뉴론의 평균 활동율은 PD 환자 보다 높았다. 하지만 촉각자극(touch)에 반응하는 nucleus ventralis caudalis (VC) 뉴론의 활동율은 ET와 PD 집단간에 차가 없었다. Bursting activity를 나타내는 뉴론은 nucleus ventralis oralis anterior (VOP)에서 ET집단이 PD 집단보다 적었다. tremor cell은 VIM에서 PD 보다 ET집단이 더 적었다. 이러한 결과는 체감각 자극에 반응하는 시상 뉴론의 특성이 운동장애의 유형에 따라 서로 다르다는 것을 시사한다.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.3
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• pp.213-221
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• 2001

The amygdala is known as a site for inducing analgesia, but its action on the trigeminal nucleus has not been known well. Little information is available on the effect of dynorphin on NMDA receptor-mediated electrophysiological events in the trigeminal nucleus. The purpose of this study was to investigate the changes in the single neuron spikes at the trigeminal nucleus caused by the amygdala and the action of dynorphin on the trigeminal nucleus. In the present study, extracellular single unit recordings were made in the dorsal horn of the medulla (trigeminal nucleus caudalis) and the effects of microiontophoretically applied compounds were examined. When [D-Ala2, N-Me-Phe4, Glys5-ol]enkephalin (DAMGO, 10-25 mM), a ${\mu}-opioid$ receptor agonist, was infused into the amygdala, the number of NMDA-evoked spikes at the trigeminal nucleus decreased. However, the application of naloxone into the trigeminal nucleus while DAMGO being infused into the amygdala increased the number of spikes. Low dose (1 mM) of dynorphin in the trigeminal nucleus produced a significant decrease in NMDA-evoked spikes of the trigeminal nucleus but the NMDA-evoked responses were facilitated by a high dose (5 mM) of dynorphin. After the ${\kappa}$ receptors were blocked with naloxone, dynorphin induced hyperalgesia. After the NMDA receptors were blocked with AP5, dynorphin induced analgesia. In conclusion, dynorphin A exerted dose-dependent dual effects (increased & decreased spike activity) on NMDA-evoked spikes in the trigeminal nucleus. The inhibitory effect of the dynorphin at a low concentration was due to the activation of ${\kappa}$ receptors and the excitatory effect at a high concentration was due to activation of NMDA receptors in the trigeminal neurons.

• The korean journal of orthodontics
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• v.28 no.3 s.68
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• pp.441-452
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• 1998

The c-fos is known as neuronal marker of second neurons which is activated by noxious peripheral stimulation. To investigate the changes of c-fos el(pression in the trigeminal nucleus complex during tooth movement, immunohistochemical study was performed. Experimental rats(9 weeks old, 210 gm 21 rats) were divided into seven groups(normal, 1 hour group, 3 hour group, 6 hour group, 12 hour group, 1 day group,3 day group). Rats in the normal group were anesthesized without orthodontic force. Rats in the experimental groups were applied orthodontic force (approximately 30 gm) to upper right maxillary molar. Frozen sections of brain stem were immunostained using rabbit antisera. The changes of c-fos expression were observed with respect to rostrocaudal distribution, laminar organization, md duration of orthodontic force application. The study results were as follows $\cdot$The c-fos nuclei in the dorsal part were observed from ipsilateral transition zone of subnucleus interpolaris and subnucleus caudalis to $C_1$ cervical dorsal horn rostrocaudally. The maximal peak point was the rostral part of subnucleus caudalis. The greatest proportion of c-fos cells were located within lamina I and II. $\cdot$The c-fos nuclei in the dorsal Part were observed from the most caudal part of subnucleus interpolaris to the middle part of the subnucleus caudalis. $\cdot$The number of c-fos immunoreactive dot increased at 1 hour group, reached its maximum at the 3 and 6 hour groups, and showed a decreasing trend after 12 hours. These results imply that nociceptive stimulation caused by continuous orthodontic force might be modulated by transition zone of subnucleus interpolaris and subnucleus caudalis, subnucleus caudalis, $C_1$ spinal dorsal hem.

• 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.

• 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.

• 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.

• Journal of Korean Neurosurgical Society
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• v.30 no.sup1
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• pp.85-90
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• 2001

Objective : DREZotomy is effective for the treatment of deafferentation pain as a consequence of root avulsion, postparaplegic pain, posttraumatic syrinx, postherpetic neuralgia, spinal cord injury, and peripheral nerve injury. We performed microsurgical DREZotomy to the patients with deafferentation pain and relieved pain without any serious complication. The purpose of this study is to evaluate the usefulness of the microsurgical DREZotomy for deafferentation pain. Methods : We evaluated 4 patients with deafferntation pain who were intractable to medical therapy. Two of them were brachial plexus injury with root avulsion owing to trauma, one was axillary metastasis of the squamous cell carcinoma of the left forearm, and the last was anesthesia dolorosa after surgical treatment(MVD and rhizotomy) of trigeminal neuralgia. Preoperative evaluation was based on the neurologic examination, radiologic imaging, and electrophysiological study. In the case of anesthesia dolorosa, we produced two parallel lesions in cephalocaudal direction, 2mm in distance, from the C2 dorsal rootlet to the 5mm superior to the obex including nucleus caudalis, after suboccipital craniectomy and C1-2 laminectomy, with use of microelectrode. In the others, we confirmed lesion site with identification of the nerve root after hemilaminectomy. We performed arachnoid dissection along the posterolateral sulcus and made lesion with microsurgical knife and microelectrocoagulation, 2mm in depth, 2mm in distance, to the direction of 30-45 degrees in the medial portion of the Lissauer's tract and the most dorsal layers of the posterior horn at the one root level above and below the lesion. Results : Compared with preoperative state, microsurgical DREZotomy significantly diminished dosage of the drugs and relieved pain meaningfully. One patient showed tansient ipsilateral ataxia, but recovered soon. There was not any serious complication. Conclusion : It may be concluded that microsurgical DREZotomy is very useful and safe therapeutic modality for deafferentation pain, especially segmentally distributed intermittent or evoke pain. Complete preoperative evaluation and proper selection of the patients and lesion making device are needed to improve the result.