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

Han J, Kwon M, Cha M, Tanioka M, Hong SK, Bai SJ, Lee BH - Neural Plast. (2015)

Bottom Line: Mechanical allodynia was significantly decreased by ZIP microinjection into the IC.The analgesic effect lasted for 12 hours.These results suggest that peripheral nerve injury induces neural plasticity related to PKMζ and that ZIP has potential applications for relieving chronic pain.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Reduction of mechanical allodynia after ZIP microinjection into the IC. (a) Identification of the ZIP injection site. ZIP was microinjected into the IC. (b) Paw withdrawal threshold to mechanical stimulation in POD 3 rats after microinjection of ZIP. Significant differences between nerve-injured and sham groups were found at the time points from 30 minutes to 12 hours after injection (∗P < 0.05). The arrow indicates the time point of ZIP or saline injection.
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fig4: Reduction of mechanical allodynia after ZIP microinjection into the IC. (a) Identification of the ZIP injection site. ZIP was microinjected into the IC. (b) Paw withdrawal threshold to mechanical stimulation in POD 3 rats after microinjection of ZIP. Significant differences between nerve-injured and sham groups were found at the time points from 30 minutes to 12 hours after injection (∗P < 0.05). The arrow indicates the time point of ZIP or saline injection.

Mentions: Figure 4(a) shows the injection site of the IC. Injection of ZIP into the IC decreased mechanical allodynia gradually on POD 3. Repeated measures two-way ANOVA indicated effects of group (F1,9 = 11.798, P < 0.01), time (F7,63 = 4.23, P < 0.01), and interaction between group and time (F7,63 = 3.93, P < 0.01). The time course of mechanical allodynia in the ZIP-injected group (n = 7) on POD 3 shows that the analgesic effects of ZIP last for 12 hours after injection (P < 0.05, unpaired t-test; Figure 4(b)), where analgesia was measured relative to the saline-injected group (n = 5). However, at 24 and 48 hours after injection, ZIP had no significant effect (P > 0.05, unpaired t-test).


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

Han J, Kwon M, Cha M, Tanioka M, Hong SK, Bai SJ, Lee BH - Neural Plast. (2015)

Reduction of mechanical allodynia after ZIP microinjection into the IC. (a) Identification of the ZIP injection site. ZIP was microinjected into the IC. (b) Paw withdrawal threshold to mechanical stimulation in POD 3 rats after microinjection of ZIP. Significant differences between nerve-injured and sham groups were found at the time points from 30 minutes to 12 hours after injection (∗P < 0.05). The arrow indicates the time point of ZIP or saline injection.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4592717&req=5

fig4: Reduction of mechanical allodynia after ZIP microinjection into the IC. (a) Identification of the ZIP injection site. ZIP was microinjected into the IC. (b) Paw withdrawal threshold to mechanical stimulation in POD 3 rats after microinjection of ZIP. Significant differences between nerve-injured and sham groups were found at the time points from 30 minutes to 12 hours after injection (∗P < 0.05). The arrow indicates the time point of ZIP or saline injection.
Mentions: Figure 4(a) shows the injection site of the IC. Injection of ZIP into the IC decreased mechanical allodynia gradually on POD 3. Repeated measures two-way ANOVA indicated effects of group (F1,9 = 11.798, P < 0.01), time (F7,63 = 4.23, P < 0.01), and interaction between group and time (F7,63 = 3.93, P < 0.01). The time course of mechanical allodynia in the ZIP-injected group (n = 7) on POD 3 shows that the analgesic effects of ZIP last for 12 hours after injection (P < 0.05, unpaired t-test; Figure 4(b)), where analgesia was measured relative to the saline-injected group (n = 5). However, at 24 and 48 hours after injection, ZIP had no significant effect (P > 0.05, unpaired t-test).

Bottom Line: Mechanical allodynia was significantly decreased by ZIP microinjection into the IC.The analgesic effect lasted for 12 hours.These results suggest that peripheral nerve injury induces neural plasticity related to PKMζ and that ZIP has potential applications for relieving chronic pain.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus