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Dysfunction of Small-Conductance Ca2+-Activated Potassium (SK) Channels Drives Amygdala Hyperexcitability and Neuropathic Pain Behaviors: Involvement of Epigenetic Mechanisms.
Yakhnitsa, Vadim; Thompson, Jeremy; Ponomareva, Olga; Ji, Guangchen; Kiritoshi, Takaki; Mahimainathan, Lenin; Molehin, Deborah; Pruitt, Kevin; Neugebauer, Volker.
Afiliação
  • Yakhnitsa V; Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
  • Thompson J; Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
  • Ponomareva O; Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
  • Ji G; Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
  • Kiritoshi T; Center of Excellence for Translational Neuroscience and Therapeutics, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
  • Mahimainathan L; Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
  • Molehin D; Department of Pathology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
  • Pruitt K; Department of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
  • Neugebauer V; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Cells ; 13(12)2024 Jun 18.
Article em En | MEDLINE | ID: mdl-38920682
ABSTRACT
Neuroplasticity in the amygdala and its central nucleus (CeA) is linked to pain modulation and pain behaviors, but cellular mechanisms are not well understood. Here, we addressed the role of small-conductance Ca2+-activated potassium (SK) channels in pain-related amygdala plasticity. The facilitatory effects of the intra-CeA application of an SK channel blocker (apamin) on the pain behaviors of control rats were lost in a neuropathic pain model, whereas an SK channel activator (NS309) inhibited pain behaviors in neuropathic rats but not in sham controls, suggesting the loss of the inhibitory behavioral effects of amygdala SK channels. Brain slice electrophysiology found hyperexcitability of CeA neurons in the neuropathic pain condition due to the loss of SK channel-mediated medium afterhyperpolarization (mAHP), which was accompanied by decreased SK2 channel protein and mRNA expression, consistent with a pretranscriptional mechanisms. The underlying mechanisms involved the epigenetic silencing of the SK2 gene due to the increased DNA methylation of the CpG island of the SK2 promoter region and the change in methylated CpG sites in the CeA in neuropathic pain. This study identified the epigenetic dysregulation of SK channels in the amygdala (CeA) as a novel mechanism of neuropathic pain-related plasticity and behavior that could be targeted to control abnormally enhanced amygdala activity and chronic neuropathic pain.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Epigênese Genética / Canais de Potássio Ativados por Cálcio de Condutância Baixa / Tonsila do Cerebelo / Neuralgia Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Epigênese Genética / Canais de Potássio Ativados por Cálcio de Condutância Baixa / Tonsila do Cerebelo / Neuralgia Idioma: En Ano de publicação: 2024 Tipo de documento: Article