Abstract

Neuropathic pain is a common problem following spinal cord injury (SCI). Effective analgesic therapy has been hampered by the lack of knowledge about the mechanisms underlying post‐SCI neuropathic pain. Current evidence suggests GABAergic spinal nociceptive processing is a critical functional node in this complex phenotype, representing a potential target for therapeutic intervention. Normal GABA neurotransmission is dependent on precise regulation of the level of intracellular chloride, which is determined by the coordinated activities of two cation/chloride cotransporters (CCCs) in the SLC12 family: the inwardly directed Na + ‐K + ‐Cl − cotransporter isoform 1 (NKCC1) and outwardly directed K + ‐Cl − cotransporter isoform 2 (KCC2). Inhibition of NKCC1 with its potent antagonist bumetanide reduces pain behavior in rats following SCI. Moreover, the injured spinal cord tissues exhibit a significant transient upregulation of NKCC1 protein and a concurrent downregulation of KCC2 protein. Thus, imbalanced function of NKCC1 and KCC2 may contribute to the induction and maintenance of the chronic neuropathic pain following SCI.

Keywords

Neuropathic painBumetanideCotransporterSpinal cord injurySpinal cordChronic painDownregulation and upregulationMedicineNeuroscienceGABAergicNociceptionPharmacologyAnesthesiaAnalgesicGene isoformInhibitory postsynaptic potentialChemistryInternal medicineReceptorPsychologyBiochemistry

MeSH Terms

AnimalsBumetanideChronic DiseaseHyperalgesiaInflammationPainRatsSodium Potassium Chloride Symporter InhibitorsSodium-Potassium-Chloride SymportersSolute Carrier Family 12Member 2Spinal Cord InjuriesSymportersTRPV Cation Channelsgamma-Aminobutyric AcidK Cl- Cotransporters

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Publication Info

Year
2010
Type
article
Volume
1198
Issue
1
Pages
168-172
Citations
130
Access
Closed

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Cite This

Tera Hasbargen, Mostafa Ahmed, Gurwattan S. Miranpuri et al. (2010). Role of NKCC1 and KCC2 in the development of chronic neuropathic pain following spinal cord injury. Annals of the New York Academy of Sciences , 1198 (1) , 168-172. https://doi.org/10.1111/j.1749-6632.2010.05462.x

Identifiers

DOI
10.1111/j.1749-6632.2010.05462.x
PMID
20536931

Data Quality

Data completeness: 81%