Abstract | Background: Methods: Neonatal mice were subjected to the MS paradigm, an established ELS model. In adulthood, the visceral pain threshold and the abdominal withdrawal reflex (AWR) were measured with an inflatable balloon. The elevated plus maze, open field test, sucrose preference test, and forced swim test were employed to evaluate the anxiety- and depression-like behaviors. The expression levels of SK2 in the spinal DH were determined by immunofluorescence and western blotting. The mRNA of SK2 and membrane palmitoylated protein 2 (MPP2) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Electrophysiology was applied to evaluate the neuronal firing rates and SK2 channel-mediated afterhyperpolarization current (I AHP). The interaction between MPP2 and SK2 was validated by coimmunoprecipitation. Results: In contrast to the naïve mice, ethological findings in MS mice revealed lowered visceral pain threshold, more evident anxiety- and depression-like behaviors, and downregulated expression of membrane SK2 protein and MPP2 protein. Moreover, electrophysiological results indicated increased neuronal firing rates and decreased I AHP in the spinal DH neurons. Nonetheless, intrathecal injection of the SK2 channel activator 1-ethyl-2-benzimidazolinone (1-EBIO) in MS mice could reverse the electrophysiological alterations and elevate the visceral pain threshold. In the naïve mice, administration of the SK2 channel blocker apamin abated I AHP and elevated spontaneous neuronal firing rates in the spinal DH neurons, reducing the visceral pain threshold. Finally, disruption of the MPP2 expression by small interfering RNA ( siRNA) could amplify visceral hypersensitivity in naïve mice. Conclusions:
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Authors | Ke Wu, Jing-Hua Gao, Rong Hua, Xiao-Han Peng, Hui Wang, Yong-Mei Zhang |
Journal | Neural plasticity
(Neural Plast)
Vol. 2020
Pg. 8876230
( 2020)
ISSN: 1687-5443 [Electronic] United States |
PMID | 33029124
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2020 Ke Wu et al. |
Chemical References |
- Kcnn2 protein, mouse
- RNA, Messenger
- Small-Conductance Calcium-Activated Potassium Channels
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Topics |
- Animals
- Down-Regulation
- Female
- Male
- Maternal Deprivation
- Mice, Inbred C57BL
- Neurons
(metabolism)
- RNA, Messenger
(metabolism)
- Small-Conductance Calcium-Activated Potassium Channels
(metabolism)
- Spinal Cord Dorsal Horn
(metabolism)
- Visceral Pain
(metabolism)
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