ReviewJAMA neurology2014
Therapeutic restoration of spinal inhibition via druggable enhancement of potassium-chloride cotransporter KCC2-mediated chloride extrusion in peripheral neuropathic pain.
Review in JAMA neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 65 citations in OpenAlex.
- Effects of whole-body vibration on neuropathic pain and the relationship between pain and spasticity in persons with spinal cord injury.Spinal cord · 2022Trial
- The Role of Serotonergic System in Parkinson's Disease-Related Pain.Neuroscience bulletin · 2026Review
- Presynaptic chloride-dependent regulation of spontaneous glutamate release in the rat medial preoptic nucleus.Frontiers in cellular neuroscience · 2026Article
- Article
- KCC2 enhancers normalize reflex responses and improve locomotor function after chronic spinal cord injury.The Journal of physiology · 2025Article
- Article
- Combined use of CLP290 and bumetanide alleviates neuropathic pain and its mechanism after spinal cord injury in rats.CNS neuroscience & therapeutics · 2024Article
- Tonic excitation by astrocytic GABA causes neuropathic pain by augmenting neuronal activity and glucose metabolism.Experimental & molecular medicine · 2024Article
- Neuronal KActa pharmacologica Sinica · 2024Review
- Development of KCC2 therapeutics to treat neurological disorders.Frontiers in molecular neuroscience · 2024Article
- Neuroinflammation in the Dorsal Root Ganglia and Dorsal Horn Contributes to Persistence of Nociceptor Sensitization in SIV-Infected Antiretroviral Therapy-Treated Macaques.The American journal of pathology · 2023Article
- Preservation of KCC2 expression in axotomized abducens motoneurons and its enhancement by VEGF.Brain structure & function · 2023Article
- Neuropathic pain: Mechanisms and therapeutic strategies.Frontiers in cell and developmental biology · 2023Review
- Discovery of Small Molecule KCC2 Potentiators Which AttenuateFrontiers in cell and developmental biology · 2022Article
- Three-Day Continuous Oxytocin Infusion Attenuates Thermal and Mechanical Nociception by Rescuing Neuronal Chloride HomeostasisFrontiers in pharmacology · 2022Article
- Long March Toward Safe and Effective Analgesia by Enhancing Gene Expression ofFrontiers in molecular neuroscience · 2022Review
- Spinal cord dorsal horn sensory gate in preclinical models of chemotherapy-induced painful neuropathy and contact dermatitis chronic itch becomes less leaky withFrontiers in molecular neuroscience · 2022Article
- The role of KCC2 and NKCC1 in spinal cord injury: From physiology to pathology.Frontiers in physiology · 2022Review
- Repurposing cancer drugs identifies kenpaullone which ameliorates pathologic pain in preclinical models via normalization of inhibitory neurotransmission.Nature communications · 2021Article
- The Alteration of Chloride Homeostasis/GABAergic Signaling in Brain Disorders: Could Oxidative Stress Play a Role?Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Peripheral neuropathic pain, typified by the development of spontaneous pain or pain hypersensitivity following injury to the peripheral nervous system, is common, greatly impairs quality of life, and is inadequately treated with available drugs. Maladaptive changes in chloride homeostasis due to a decrease in the functional expression of the potassium-chloride cotransporter KCC2 in spinal cord dorsal horn neurons are a major contributor to the central disinhibition of γ-aminobutyric acid type A receptor- and glycine receptor-mediated signaling that characterizes neuropathic pain. A compelling novel analgesic strategy is to restore spinal ionotropic inhibition by enhancing KCC2-mediated chloride extrusion. We review the data on which this theory of alternative analgesia is based, discuss recent high-throughput screens that have searched for small-molecule activators of KCC2, and propose other strategies of KCC2 activation based on recent developments in the basic understanding of KCC2's functional regulation. Exploiting the chloride-dependent functional plasticity of the γ-aminobutyric acid and glycinergic system by targeting KCC2 may be a tenable method of restoring ionotropic inhibition not only in neuropathic pain but also in other "hyperexcitable" diseases of the nervous system such as seizures and spasticity.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.