The Role of K+-Cl−-Cotransporter-2 in Neuropathic Pain

The pain sensory system normally functions under a fine balance between excitation and inhibition. When this balance is perturbed for some reason, it leads to neuropathic pain. There is accumulating evidence that attributes this pain generation to specific dysfunctions of the inhibitory system in th...

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Bibliographic Details
Published in:Neurochemical research 2018, Vol.43 (1), p.110-115
Main Author: Kitayama, Tomoya
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biomedicine
Cell Biology
Chlorides
GABAergic Neurons - metabolism
Humans
K Cl- Cotransporters
Low level
Neuralgia - metabolism
Neuralgia - physiopathology
Neurochemistry
Neurology
Neurosciences
Original Paper
Pain
Peripheral Nerve Injuries - metabolism
Peripheral Nerve Injuries - physiopathology
Peripheral neuropathy
Potassium
Potassium-chloride cotransporter
Spinal cord
Spinal Cord - metabolism
Spinal Cord - physiopathology
Symporters - metabolism
Synaptic Transmission - genetics
γ-Aminobutyric acid
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Summary:The pain sensory system normally functions under a fine balance between excitation and inhibition. When this balance is perturbed for some reason, it leads to neuropathic pain. There is accumulating evidence that attributes this pain generation to specific dysfunctions of the inhibitory system in the spinal cord. One possible mechanism leading to the induction of these dysfunctions is the down-regulation of K + -Cl − -cotransporter-2 (KCC2) expression. In fact, various neuropathic pain models indicate a decrease of KCC2 expression in the spinal cord. The alteration of KCC2 expression affects GABAergic and glycinergic neurotransmissions, because KCC2 is a potassium-chloride exporter and serves to maintain intracellular chloride concentration. When there is a low level of KCC2 expression, GABAergic and glycinergic neurotransmissions transform from inhibitory signals to excitatory signals. In this review, the hypothesis that an alteration of KCC2 expression has a crucial influence on the initiation/development or maintenance of neuropathic pain is discussed. In addition, it is suggested that the alteration of inhibitory signals is dependent on the time after peripheral nerve injury.
ISSN:0364-3190
1573-6903
DOI:10.1007/s11064-017-2344-3