Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury

The insular cortex (IC) is associated with important functions linked with pain and emotions. According to recent reports, neural plasticity in the brain including the IC can be induced by nerve injury and may contribute to chronic pain. Continuous active kinase, protein kinase Mζ (PKMζ), has been k...

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Main Authors: Jeongsoo Han, Minjee Kwon, Myeounghoon Cha, Motomasa Tanioka, Seong-Karp Hong, Sun Joon Bai, Bae Hwan Lee
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2015/601767
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author Jeongsoo Han
Minjee Kwon
Myeounghoon Cha
Motomasa Tanioka
Seong-Karp Hong
Sun Joon Bai
Bae Hwan Lee
author_facet Jeongsoo Han
Minjee Kwon
Myeounghoon Cha
Motomasa Tanioka
Seong-Karp Hong
Sun Joon Bai
Bae Hwan Lee
author_sort Jeongsoo Han
collection DOAJ
description The insular cortex (IC) is associated with important functions linked with pain and emotions. According to recent reports, neural plasticity in the brain including the IC can be induced by nerve injury and may contribute to chronic pain. Continuous active kinase, protein kinase Mζ (PKMζ), has been known to maintain the long-term potentiation. This study was conducted to determine the role of PKMζ in the IC, which may be involved in the modulation of neuropathic pain. Mechanical allodynia test and immunohistochemistry (IHC) of zif268, an activity-dependent transcription factor required for neuronal plasticity, were performed after nerve injury. After ζ-pseudosubstrate inhibitory peptide (ZIP, a selective inhibitor of PKMζ) injection, mechanical allodynia test and immunoblotting of PKMζ, phospho-PKMζ (p-PKMζ), and GluR1 and GluR2 were observed. IHC demonstrated that zif268 expression significantly increased in the IC after nerve injury. Mechanical allodynia was significantly decreased by ZIP microinjection into the IC. The analgesic effect lasted for 12 hours. Moreover, the levels of GluR1, GluR2, and p-PKMζ were decreased after ZIP microinjection. These results suggest that peripheral nerve injury induces neural plasticity related to PKMζ and that ZIP has potential applications for relieving chronic pain.
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spelling doaj-art-8811e236b8564f999131209ee220cc722025-02-03T01:22:31ZengWileyNeural Plasticity2090-59041687-54432015-01-01201510.1155/2015/601767601767Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve InjuryJeongsoo Han0Minjee Kwon1Myeounghoon Cha2Motomasa Tanioka3Seong-Karp Hong4Sun Joon Bai5Bae Hwan Lee6Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Republic of KoreaDepartment of Physiology, Yonsei University College of Medicine, Seoul 120-752, Republic of KoreaDepartment of Physiology, Yonsei University College of Medicine, Seoul 120-752, Republic of KoreaDepartment of Physiology, Yonsei University College of Medicine, Seoul 120-752, Republic of KoreaDivision of Bio and Health Sciences, Mokwon University, Daejeon 302-729, Republic of KoreaDepartment of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of KoreaDepartment of Physiology, Yonsei University College of Medicine, Seoul 120-752, Republic of KoreaThe insular cortex (IC) is associated with important functions linked with pain and emotions. According to recent reports, neural plasticity in the brain including the IC can be induced by nerve injury and may contribute to chronic pain. Continuous active kinase, protein kinase Mζ (PKMζ), has been known to maintain the long-term potentiation. This study was conducted to determine the role of PKMζ in the IC, which may be involved in the modulation of neuropathic pain. Mechanical allodynia test and immunohistochemistry (IHC) of zif268, an activity-dependent transcription factor required for neuronal plasticity, were performed after nerve injury. After ζ-pseudosubstrate inhibitory peptide (ZIP, a selective inhibitor of PKMζ) injection, mechanical allodynia test and immunoblotting of PKMζ, phospho-PKMζ (p-PKMζ), and GluR1 and GluR2 were observed. IHC demonstrated that zif268 expression significantly increased in the IC after nerve injury. Mechanical allodynia was significantly decreased by ZIP microinjection into the IC. The analgesic effect lasted for 12 hours. Moreover, the levels of GluR1, GluR2, and p-PKMζ were decreased after ZIP microinjection. These results suggest that peripheral nerve injury induces neural plasticity related to PKMζ and that ZIP has potential applications for relieving chronic pain.http://dx.doi.org/10.1155/2015/601767
spellingShingle Jeongsoo Han
Minjee Kwon
Myeounghoon Cha
Motomasa Tanioka
Seong-Karp Hong
Sun Joon Bai
Bae Hwan Lee
Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury
Neural Plasticity
title Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury
title_full Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury
title_fullStr Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury
title_full_unstemmed Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury
title_short Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury
title_sort plasticity related pkmζ signaling in the insular cortex is involved in the modulation of neuropathic pain after nerve injury
url http://dx.doi.org/10.1155/2015/601767
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