title: Plasticity-Related PKMζ Signaling in the Insular Cortex Is Involved in the Modulation of Neuropathic Pain after Nerve Injury.
abstract: 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.
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea ; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Jeongsoo
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea ; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Minjee
authors.initials: M
authors.lastname: Kwon
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Myeounghoon
authors.initials: M
authors.lastname: Cha
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea ; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Motomasa
authors.initials: M
authors.lastname: Tanioka
authors.affiliation: Division of Bio and Health Sciences, Mokwon University, Daejeon 302-729, Republic of Korea.
authors.forename: Seong-Karp
authors.initials: SK
authors.lastname: Hong
authors.affiliation: Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Sun Joon
authors.initials: SJ
authors.lastname: Bai
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea ; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Bae Hwan
authors.initials: BH
authors.lastname: Lee
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D057846:Cell-Penetrating Peptides; D002540:Cerebral Cortex / Q000201:enzymology* / Q000503:physiopathology*; D051766:Early Growth Response Protein 1 / Q000235:genetics; D051273:Glucose Transporter Type 2 / Q000235:genetics; D006930:Hyperalgesia / Q000503:physiopathology / Q000523:psychology; D055666:Lipopeptides / Q000494:pharmacology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009437:Neuralgia / Q000201:enzymology / Q000503:physiopathology*; D009473:Neuronal Plasticity; D010147:Pain Measurement / Q000187:drug effects; D059348:Peripheral Nerve Injuries / Q000201:enzymology / Q000503:physiopathology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics; D015398:Signal Transduction
chemical_list: D034961:Antigens, Nuclear; D057846:Cell-Penetrating Peptides; D051766:Early Growth Response Protein 1; D051273:Glucose Transporter Type 2; D055666:Lipopeptides; D009419:Nerve Tissue Proteins; D011493:Protein Kinase C; D018091:Receptors, AMPA; C486110:Egr1 protein, rat; C546339:Rbfox3 protein, rat; C495682:Slc2a2 protein, mouse; C568285:zeta-inhibitory peptide; C504730:protein kinase M zeta, rat