KCC2-GABAA pathway correlates with the analgesic effect of electro-acupuncture in CCI rats

Potassium-chloride cotransporter 2 (KCC2) has been indicated to serve a crucial role during chronic neuropathic pain (NP). Following the emergence of NP, γ-aminobutyric acid (GABA) A receptor-mediated signaling may be further impaired by the changes of KCC2 chloride anion gradient. In the present study, the authors investigate the effect of electro-acupuncture (EA) on the behavior and the expression of KCC2 and GABAA receptor γ2 subunit in the spinal cord of chronic constriction injury (CCI) model rats. A total of 60 adult male Sprague-Dawley rats were divided into four groups: Normal group, sham-CCI group, CCI group and CCI+EA group. The effect of EA was assessed via the values of mechanical withdrawal threshold and thermal withdrawal latency, which were significantly improved upon stimulation of the ST-36 and GB-34 acupoints. In addition, a marked reduction in both the mRNA and protein levels of KCC2 and GABAA receptor γ2 subunit was observed in the spinal cord following loose ligation of the sciatic nerve. The reductions in KCC2 and GABAA receptor γ2 subunit expression were reversed by EA treatment. These results support the notion that KCC2 and GABAA receptor γ2 subunit contribute to NP following peripheral nerve injury and extend the understanding of the analgesic effects of EA on NP.

• Publication year

  2018

• Venue

  Molecular Medicine Reports

• Publication date

  2018-03-16

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.3892/mmr.2018.8766PMID 29568893PMCID 5928653
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2012cited by this paper
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  2012cited by this paper
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  2012cited by this paper
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  2012cited by this paper
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  2011cited by this paper
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  2011cited by this paper
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  2010cited by this paper
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  2010cited by this paper
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  2009cited by this paper
• Chloride regulation in the pain pathway.

  2009cited by this paper
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  2008cited by this paper
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  2008cited by this paper
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  2008cited by this paper
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  2008cited by this paper
• Loose ligation of the sciatic nerve is associated with TrkB receptor‐dependent decreases in KCC2 protein levels in the ipsilateral spinal dorsal horn

  2008cited by this paper
• Altered chloride homeostasis in neurological disorders: a new target.

  2007cited by this paper
• Expression changes of cation chloride cotransporters in the rat spinal cord following intraplantar formalin.

  2006cited by this paper
• Role of cation-chloride-cotransporters (CCC) in pain and hyperalgesia.

  2005cited by this paper
• BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain

  2005cited by this paper
• Effects of synchronous or asynchronous electroacupuncture stimulation with low versus high frequency on spinal opioid release and tail flick nociception.

  2005cited by this paper
• Production and Release of Neuroprotective Tumor Necrosis Factor by P2X7 Receptor-Activated Microglia

  2004cited by this paper
• Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain

  2003influential reference
• Subunit composition, distribution and function of GABA(A) receptor subtypes.

  2002cited by this paper
• Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.

  2001cited by this paper
• The role of central and peripheral Cannabinoid1 receptors in the antihyperalgesic activity of cannabinoids in a model of neuropathic pain

  2001cited by this paper
• Cation-Chloride Cotransporters in Neuronal Communication.

  2000cited by this paper
• theta, a novel gamma-aminobutyric acid type A receptor subunit.

  1999cited by this paper
• Neuropathic pain: aetiology, symptoms, mechanisms, and management.

  1999cited by this paper
• International Union of Pharmacology. XV. Subtypes of gamma-aminobutyric acidA receptors: classification on the basis of subunit structure and receptor function.

  1998cited by this paper
• Electroacupuncture: mechanisms and clinical application.

  1998cited by this paper
• Localization of GABAA-receptor gamma 2-subunit mRNA-containing neurons in the rat central nervous system.

  1992cited by this paper
• Functional characteristics and sites of gene expression of the alpha 1, beta 1, gamma 2-isoform of the rat GABAA receptor

  1990cited by this paper
• GABAA and GABAB receptor site distribution in the rat central nervous system.

  1987cited by this paper
• Stress-induced analgesia: adaptive pain suppression.

  1986cited by this paper

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  2025cites this paper
• Therapeutic efficacy of acupuncture point stimulation for stomach cancer pain: a systematic review and meta-analysis

  2024cites this paper
• Acupuncture for insomnia symptoms in hypertensive patients: a systematic review and meta-analysis

  2024cites this paper
• EA participates in pain transition through regulating KCC2 expression by BDNF-TrkB in the spinal cord dorsal horn of male rats

  2023cites this paper
• Molecular mechanism of electroacupuncture for improving perioperative complications with the guidance of enhanced recovery after surgery

  2023cites this paper
• The mechanistic basis for the effects of electroacupuncture on neuropathic pain within the central nervous system.

  2023cites this paper
• Role of nerve signal transduction and neuroimmune crosstalk in mediating the analgesic effects of acupuncture for neuropathic pain

  2023cites this paper
• Effective Oriental Magic for Analgesia: Acupuncture

  2022cites this paper
• Electroacupuncture suppresses spinal nerve ligation-induced neuropathic pain via regulation of synaptic plasticity through upregulation of basic fibroblast growth factor expression

  2022cites this paper
• Long March Toward Safe and Effective Analgesia by Enhancing Gene Expression of Kcc2: First Steps Taken

  2022cites this paper
• Combined-Acupoint Electroacupuncture Induces Better Analgesia via Activating the Endocannabinoid System in the Spinal Cord

  2022cites this paper
• Research Hotspots and Trends on Acupuncture for Neuropathic Pain: A Bibliometric Analysis from 2002 to 2021

  2022cites this paper
• Role of GABAAR in the Transition From Acute to Chronic Pain and the Analgesic Effect of Electroacupuncture on Hyperalgesic Priming Model Rats

  2021cites this paper
• Progress on the Experimental Research of Sciatic Nerve Injury with Acupuncture

  2021cites this paper
• The Role of Neuroglial Crosstalk and Synaptic Plasticity-Mediated Central Sensitization in Acupuncture Analgesia

  2021cites this paper
• Needling Interventions for Sciatica: Choosing Methods Based on Neuropathic Pain Mechanisms—A Scoping Review

  2021cites this paper
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  2021cites this paper
• Electroacupuncture improves neuronal plasticity through the A2AR/cAMP/PKA signaling pathway in SNL rats.

  2021cites this paper
• Genetic and environmental regulators of Kcc2/KCC2 gene expression

  2020cites this paper
• The Expanding Therapeutic Potential of Neuronal KCC2

  2020cites this paper
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  2019cites this paper
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  2019cites this paper