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11. Selectively targeting pain in the trigeminal system

Author

Kim, Hyun Yeong, Kim, Kihwan, Li, Hai Ying, Chung, Gehoon, Park, Chul-Kyu, Kim, Joong Soo, Jung, Sung Jun, Lee, Min Kyung, Ahn, Dong Kuk, Hwang, Se Jin, Kang, Youngnam, Binshtok, Alexander M., Bean, Bruce P., Woolf, Clifford J., and Oh, Seog Bae

Published
2010
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16. Early Blockade of EphA4 Pathway Reduces Trigeminal Neuropathic Pain

Author

Kim, Min-Ji, Son, Jo-Young, Ju, Jin-Sook, and Ahn, Dong-Kuk

Subjects
neuropathic pain, siRNA, EphA4, trigeminal, Journal of Pain Research, Original Research, ephrin, allodynia
Abstract

Min-Ji Kim,* Jo-Young Son,* Jin-Sook Ju, Dong-Kuk Ahn Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Korea*These authors contributed equally to this workCorrespondence: Dong-Kuk AhnDepartment of Oral Physiology, School of Dentistry, Kyungpook National University, 2177 Dalgubeol-daero, Chung-gu, Daegu 41940, KoreaTel +82-53-660-6840Fax +82-53-421-4077Email dkahn@knu.ac.krBackground: Although the Eph receptor plays an important role in the development of neuropathic pain following nerve injury, there has been no evidence of the participation of the ephrin A4 receptor (EphA4) in the development of trigeminal neuropathic pain. The present study investigated the role of EphA4 in central nociceptive processing in rats with inferior alveolar nerve injury.Materials and Methods: Male Sprague-Dawley rats were used in all our experiments. A rat model for trigeminal neuropathic pain was produced using malpositioned dental implants. The left mandibular second molar was extracted under anesthesia, followed by the placement of a miniature dental implant to injure the inferior alveolar nerve.Results: Our current findings show that nerve injury induced by malpositioned dental implants evokes significant mechanical allodynia and up-regulation of EphA4 expression in the ipsilateral trigeminal subnucleus caudalis. Although daily treatment with EphA4-Fc, an EphA4 antagonist, did not produce prolonged anti-allodynic effects after the chronic neuropathic pain had been already established, an early treatment protocol with repeated EphA4-Fc administration significantly attenuated mechanical allodynia before initiation of chronic neuropathic pain. Finally, we confirmed the participation of the central EphA4 pathway in the development of trigeminal neuropathic pain by reducing EphA4 expression using EphA4 siRNA. This suppression of EphA4 produced significantly prolonged anti-allodynic effects.Conclusion: These results suggest that early blockade of central EphA4 signaling provides a new therapeutic target for the treatment of trigeminal neuropathic pain.Keywords: neuropathic pain, ephrin, EphA4, siRNA, allodynia, trigeminal

Published
2020

17. Early Blockade of EphA4 Pathway Reduces Trigeminal Neuropathic Pain

Author

Kim,Min-Ji, Son,Jo-Young, Ju,Jin-Sook, Ahn,Dong-Kuk, Kim,Min-Ji, Son,Jo-Young, Ju,Jin-Sook, and Ahn,Dong-Kuk

Abstract

Min-Ji Kim,* Jo-Young Son,* Jin-Sook Ju, Dong-Kuk Ahn Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Korea*These authors contributed equally to this workCorrespondence: Dong-Kuk AhnDepartment of Oral Physiology, School of Dentistry, Kyungpook National University, 2177 Dalgubeol-daero, Chung-gu, Daegu 41940, KoreaTel +82-53-660-6840Fax +82-53-421-4077Email dkahn@knu.ac.krBackground: Although the Eph receptor plays an important role in the development of neuropathic pain following nerve injury, there has been no evidence of the participation of the ephrin A4 receptor (EphA4) in the development of trigeminal neuropathic pain. The present study investigated the role of EphA4 in central nociceptive processing in rats with inferior alveolar nerve injury.Materials and Methods: Male Sprague-Dawley rats were used in all our experiments. A rat model for trigeminal neuropathic pain was produced using malpositioned dental implants. The left mandibular second molar was extracted under anesthesia, followed by the placement of a miniature dental implant to injure the inferior alveolar nerve.Results: Our current findings show that nerve injury induced by malpositioned dental implants evokes significant mechanical allodynia and up-regulation of EphA4 expression in the ipsilateral trigeminal subnucleus caudalis. Although daily treatment with EphA4-Fc, an EphA4 antagonist, did not produce prolonged anti-allodynic effects after the chronic neuropathic pain had been already established, an early treatment protocol with repeated EphA4-Fc administration significantly attenuated mechanical allodynia before initiation of chronic neuropathic pain. Finally, we confirmed the participation of the central EphA4 pathway in the development of trigeminal neuropathic pain by reducing EphA4 expression using EphA4 siRNA. This suppression of EphA4 produced significantly prolonged anti-allodynic effects.Conclusion: These results suggest that early blockade of c

Published
2020

29. Central ANG II-receptor antagonists impair cardiovascular and vasopressin response to hemorrhage in rats

Author

Lee, Won-Jung, Yang, Eun-Ktoung, Ahn, Dong-kuk, Park, Yoon-Yub, Kim, Hyeong-Jin, and Park, Jae-Sik

Subjects
Hemorrhage -- Research, Angiotensin -- Physiological aspects, Biological sciences
Abstract

A study is conducted on conscious spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) and Wistar rats to determine the impairment of vasopressin and cardiovascular response to angiotensin II antagonists. The fall in blood pressure is higher during and after hemorrhage when losartan and saralasin are injected intracerebroventricularly in SHR and Wistar rats. Less vasopressin and more renin are released by intracerebroventricular angiotensin II antagonists after hemorrhage. No changes are observed in WKY rats.

Published
1995

31. Signal Transduction Mechanisms Underlying Group I mGluR-mediated Increase in Frequency and Amplitude of Spontaneous EPSCs in the Spinal Trigeminal Subnucleus Oralis of the Rat

Author

Ahn Dong-Kuk, Han Seung-Ro, Han Sang-Mi, Park Eun-Sung, Song Ji-Hyeon, and Youn Dong-Ho

Subjects
Pathology, RB1-214
Abstract

Abstract Group I mGluRs (mGluR1 and 5) pre- and/or postsynaptically regulate synaptic transmission at glutamatergic synapses. By recording spontaneous EPSCs (sEPSCs) in the spinal trigeminal subnucleus oralis (Vo), we here investigated the regulation of glutamatergic transmission through the activation of group I mGluRs. Bath-applied DHPG (10 μM/5 min), activating the group I mGluRs, increased sEPSCs both in frequency and amplitude; particularly, the increased amplitude was long-lasting. The DHPG-induced increases of sEPSC frequency and amplitude were not NMDA receptor-dependent. The DHPG-induced increase in the frequency of sEPSCs, the presynaptic effect being further confirmed by the DHPG effect on paired-pulse ratio of trigeminal tract-evoked EPSCs, an index of presynaptic modulation, was significantly but partially reduced by blockades of voltage-dependent sodium channel, mGluR1 or mGluR5. Interestingly, PKC inhibition markedly enhanced the DHPG-induced increase of sEPSC frequency, which was mainly accomplished through mGluR1, indicating an inhibitory role of PKC. In contrast, the DHPG-induced increase of sEPSC amplitude was not affected by mGluR1 or mGluR5 antagonists although the long-lasting property of the increase was disappeared; however, the increase was completely inhibited by blocking both mGluR1 and mGluR5. Further study of signal transduction mechanisms revealed that PLC and CaMKII mediated the increases of sEPSC in both frequency and amplitude by DHPG, while IP3 receptor, NO and ERK only that of amplitude during DHPG application. Altogether, these results indicate that the activation of group I mGluRs and their signal transduction pathways differentially regulate glutamate release and synaptic responses in Vo, thereby contributing to the processing of somatosensory signals from orofacial region.

Published
2009
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41. Baicalin Activates Glycine and -Aminobutyric Acid Receptors on Substantia Gelatinosa Neurons of the Trigeminal Subsnucleus Caudalis in Juvenile Mice.

Author

Yin, Hua, Bhattarai, Janardhan Prasad, Oh, Sun Mi, Park, Soo Joung, Ahn, Dong Kuk, and Han, Seong Kyu

Subjects
AMINOBUTYRIC acid, ANIMAL experimentation, BRAIN, BRAIN stem, CELL receptors, CHLORIDES, ELECTROPHYSIOLOGY, FLUMAZENIL, GABA antagonists, GLYCINE, GLYCOSIDES, RESEARCH methodology, BOTANIC medicine, MEMBRANE proteins, MICE, NEURONS, PAIN, PROBABILITY theory, RESEARCH funding, SODIUM, STATISTICS, STRYCHNINE, T-test (Statistics), TISSUE culture, DATA analysis, PRE-tests & post-tests, DATA analysis software, FLAVONES, DESCRIPTIVE statistics, ONE-way analysis of variance
Abstract

The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) receives nociceptive afferent inputs from thin-myelinated A fibers and unmyelinated C fibers and has been shown to be involved in the processing of orofacial nociceptive information. Scutellaria baicalensis Georgi (Huang-Qin, SbG), one of the 50 fundamental herbs of Chinese herbology, has been used historically as anti-inflammatory and antineoplastic medicine. Baicalin, one of the major compounds of SbG, has been reported to have neuroprotective, anti-inflammatory and analgesic effects. However, the receptor type activated by baicalin and its precise action mechanism on the SG neurons of Vc have not yet been studied. The whole-cell patch clamp technique was performed to examine the ion channels activated by baicalin on the SG neurons of Vc. In high Cl pipette solution, the baicalin (300M) induced repeatable inward currents (pA, ) without desensitization on all the SG neurons tested. Further, the inward currents showed a concentration (0.1-3mM) dependent pattern. The inward current was sustained in the presence of tetrodotoxin (0.5M), a voltage sensitive Na channel blocker. In addition, baicalin-induced inward currents were reduced in the presence of picrotoxin (50M), a GABAA receptor antagonist, flumazenil (100M), a benzodiazepine-sensitive GABAA receptor antagonist, and strychnine (2M), a glycine receptor antagonist, respectively. These results indicate that baicalin has inhibitory effects on the SG neurons of the Vc, which are due to the activation of GABAA and/or the glycine receptor. Our results suggest that baicalin may be a potential target for orofacial pain modulation. [ABSTRACT FROM AUTHOR]

Published
2016
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43. ESM-1 regulates cell growth and metastatic process through activation of NF-κB in colorectal cancer

Author

Kang, Yun Hee, primary, Ji, Na Young, additional, Han, Seung Ro, additional, Lee, Chung Il, additional, Kim, Jae Wha, additional, Yeom, Young Il, additional, Kim, Young Ho, additional, Chun, Ho Kyung, additional, Kim, Jong Wan, additional, Chung, Jin Woong, additional, Ahn, Dong Kuk, additional, Lee, Hee Gu, additional, and Song, Eun Young, additional

Published
2012
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