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Early Blockade of EphA4 Pathway Reduces Trigeminal Neuropathic Pain

BACKGROUND: 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...

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Autores principales: Kim, Min-Ji, Son, Jo-Young, Ju, Jin-Sook, Ahn, Dong-Kuk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250313/
https://www.ncbi.nlm.nih.gov/pubmed/32547180
http://dx.doi.org/10.2147/JPR.S249185
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author Kim, Min-Ji
Son, Jo-Young
Ju, Jin-Sook
Ahn, Dong-Kuk
author_facet Kim, Min-Ji
Son, Jo-Young
Ju, Jin-Sook
Ahn, Dong-Kuk
author_sort Kim, Min-Ji
collection PubMed
description BACKGROUND: 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.
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spelling pubmed-72503132020-06-15 Early Blockade of EphA4 Pathway Reduces Trigeminal Neuropathic Pain Kim, Min-Ji Son, Jo-Young Ju, Jin-Sook Ahn, Dong-Kuk J Pain Res Original Research BACKGROUND: 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. Dove 2020-05-22 /pmc/articles/PMC7250313/ /pubmed/32547180 http://dx.doi.org/10.2147/JPR.S249185 Text en © 2020 Kim et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Kim, Min-Ji
Son, Jo-Young
Ju, Jin-Sook
Ahn, Dong-Kuk
Early Blockade of EphA4 Pathway Reduces Trigeminal Neuropathic Pain
title Early Blockade of EphA4 Pathway Reduces Trigeminal Neuropathic Pain
title_full Early Blockade of EphA4 Pathway Reduces Trigeminal Neuropathic Pain
title_fullStr Early Blockade of EphA4 Pathway Reduces Trigeminal Neuropathic Pain
title_full_unstemmed Early Blockade of EphA4 Pathway Reduces Trigeminal Neuropathic Pain
title_short Early Blockade of EphA4 Pathway Reduces Trigeminal Neuropathic Pain
title_sort early blockade of epha4 pathway reduces trigeminal neuropathic pain
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250313/
https://www.ncbi.nlm.nih.gov/pubmed/32547180
http://dx.doi.org/10.2147/JPR.S249185
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