Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain

Jeffrey A. M. Coull, Dominic Boudreau, Karine Bachand, Steven A. Prescott, Francine Nault, Attila Sík, Paul De Koninck and Yves De Koninck ()
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Jeffrey A. M. Coull: Neurobiologie Cellulaire, Centre de recherche Université Laval Robert-Giffard
Dominic Boudreau: Neurobiologie Cellulaire, Centre de recherche Université Laval Robert-Giffard
Karine Bachand: Neurobiologie Cellulaire, Centre de recherche Université Laval Robert-Giffard
Steven A. Prescott: Neurobiologie Cellulaire, Centre de recherche Université Laval Robert-Giffard
Francine Nault: Neurobiologie Cellulaire, Centre de recherche Université Laval Robert-Giffard
Attila Sík: Neurobiologie Cellulaire, Centre de recherche Université Laval Robert-Giffard
Paul De Koninck: Neurobiologie Cellulaire, Centre de recherche Université Laval Robert-Giffard
Yves De Koninck: Neurobiologie Cellulaire, Centre de recherche Université Laval Robert-Giffard

Nature, 2003, vol. 424, issue 6951, 938-942

Abstract: Abstract Modern pain-control theory1 predicts that a loss of inhibition (disinhibition) in the dorsal horn of the spinal cord is a crucial substrate for chronic pain syndromes2. However, the nature of the mechanisms that underlie such disinhibition has remained controversial3,4,5,6. Here we present evidence for a novel mechanism of disinhibition following peripheral nerve injury. It involves a trans-synaptic reduction in the expression of the potassium–chloride exporter KCC2, and the consequent disruption of anion homeostasis in neurons of lamina I of the superficial dorsal horn, one of the main spinal nociceptive output pathways7. In our experiments, the resulting shift in the transmembrane anion gradient caused normally inhibitory anionic synaptic currents to be excitatory, substantially driving up the net excitability of lamina I neurons. Local blockade or knock-down of the spinal KCC2 exporter in intact rats markedly reduced the nociceptive threshold, confirming that the reported disruption of anion homeostasis in lamina I neurons was sufficient to cause neuropathic pain.

Date: 2003
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DOI: 10.1038/nature01868

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