ArticleAnesthesia and analgesia2011
Inhibition of KCC2 in mouse spinal cord neurons leads to hypersensitivity to thermal stimulation.
Article in Anesthesia and analgesia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Rate-Dependent Depression of the Hoffmann Reflex: Practical Applications in Painful Diabetic Neuropathy.Diabetes & metabolism journal · 2024Review
- Long March Toward Safe and Effective Analgesia by Enhancing Gene Expression ofFrontiers in molecular neuroscience · 2022Review
- Orexinergic descending inhibitory pathway mediates linalool odor-induced analgesia in mice.Scientific reports · 2021Article
- LIFU Alleviates Neuropathic Pain by Improving the KCCNeural plasticity · 2021Article
- Rehabilitation Decreases Spasticity by Restoring Chloride Homeostasis through the Brain-Derived Neurotrophic Factor-KCC2 Pathway after Spinal Cord Injury.Journal of neurotrauma · 2020Article
- Dexmedetomidine attenuates persistent postsurgical pain by upregulating KJournal of pain research · 2018Article
- Intrathecal Injection of Human Umbilical Cord-Derived Mesenchymal Stem Cells Ameliorates Neuropathic Pain in Rats.Neurochemical research · 2016Article
- Interleukin-17A Acts to Maintain Neuropathic Pain Through Activation of CaMKII/CREB Signaling in Spinal Neurons.Molecular neurobiology · 2016Article
- Engagement of the GABA to KCC2 signaling pathway contributes to the analgesic effects of A3AR agonists in neuropathic pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Expanding Spectrum of Sodium Potassium Chloride Co-transporters in the Pathophysiology of Diseases.Current neuropharmacology · 2015Review
- Syndrome of severe pain associated with a continuous bumetanide infusion.International journal of cardiology · 2014Article
- In silico analysis and experimental verification of OSR1 kinase - Peptide interaction.Journal of structural biology · 2014Article
- Therapeutic restoration of spinal inhibition via druggable enhancement of potassium-chloride cotransporter KCC2-mediated chloride extrusion in peripheral neuropathic pain.JAMA neurology · 2014Review
- Ovariectomy modulation of morphine analgesia of neuropathic pain is associated with the change of K(+)-Cl(-) cotransporter 2 protein level in spinal dorsal horn.International journal of clinical and experimental medicine · 2014Article
- Neuroinflammation and comorbidity of pain and depression.Pharmacological reviews · 2014Review
- Physiology of SLC12 transporters: lessons from inherited human genetic mutations and genetically engineered mouse knockouts.American journal of physiology. Cell physiology · 2013Review
- Molecular physiology of SPAK and OSR1: two Ste20-related protein kinases regulating ion transport.Physiological reviews · 2012Review
- Further optimization of the K-Cl cotransporter KCC2 antagonist ML077: development of a highly selective and more potent in vitro probe.Bioorganic & medicinal chemistry letters · 2012Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundKCC2, a neuronal-specific K-Cl cotransporter, is involved in pain perception physiology through its effects on postsynaptic inhibition in spinal cord neurons. We injected a newly identified, highly potent and selective inhibitor of KCC2 (D4), an inactive structural variant (D4.14), and the Na-K-2Cl cotransporter (NKCC1) inhibitor, bumetanide, into the intrathecal space of mice to measure their effect on heat-evoked nociceptive responses.
methodsCommercially available intrathecal catheters were modified and surgically placed into 2 cohorts of 10 mice. After recovery from the procedure, the mice were injected with D4, D4.14, and bumetanide through this catheter. Nociceptive measurements (hotplate assay, tail flick assay) were performed after injection of each of the test drugs and compared with vehicle controls.
resultsTwo mice in each cohort were omitted because of postprocedure complications. There was a statistically significant decrease (P < 0.01) in withdrawal latency after injection of the active KCC2 inhibitor but not after injection of the inactive compound (P = 0.78), as measured by hotplate assay at 55°C. Injection of bumetanide significantly increased withdrawal latency (P = 0.02) at the same temperature. These results were confirmed using tail flick assays performed at 49°C.
conclusionsInhibition of KCC2 by D4 led to decreased heat-evoked withdrawal latency in mice, as measured by hotplate and tail flick assays, whereas inhibition of NKCC1 by bumetanide resulted in increased response latencies to heat stimuli as measured by both of these nociceptive tests.
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