PMID- 20536931 OWN - NLM STAT- MEDLINE DCOM- 20100707 LR - 20231213 IS - 1749-6632 (Electronic) IS - 0077-8923 (Linking) VI - 1198 DP - 2010 Jun TI - Role of NKCC1 and KCC2 in the development of chronic neuropathic pain following spinal cord injury. PG - 168-72 LID - 10.1111/j.1749-6632.2010.05462.x [doi] AB - 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. FAU - Hasbargen, Tera AU - Hasbargen T AD - Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. FAU - Ahmed, Mostafa M AU - Ahmed MM FAU - Miranpuri, Gurwattan AU - Miranpuri G FAU - Li, Lin AU - Li L FAU - Kahle, Kristopher T AU - Kahle KT FAU - Resnick, Daniel AU - Resnick D FAU - Sun, Dandan AU - Sun D LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Ann N Y Acad Sci JT - Annals of the New York Academy of Sciences JID - 7506858 RN - 0 (Slc12a2 protein, rat) RN - 0 (Sodium Potassium Chloride Symporter Inhibitors) RN - 0 (Sodium-Potassium-Chloride Symporters) RN - 0 (Solute Carrier Family 12, Member 2) RN - 0 (Symporters) RN - 0 (TRPV Cation Channels) RN - 0 (Trpv1 protein, rat) RN - 0Y2S3XUQ5H (Bumetanide) RN - 56-12-2 (gamma-Aminobutyric Acid) SB - IM MH - Animals MH - Bumetanide/pharmacology MH - Chronic Disease MH - Hyperalgesia/*physiopathology MH - Inflammation/physiopathology MH - Pain/*physiopathology MH - Rats MH - Sodium Potassium Chloride Symporter Inhibitors/pharmacology MH - Sodium-Potassium-Chloride Symporters/drug effects/genetics/*physiology MH - Solute Carrier Family 12, Member 2 MH - Spinal Cord Injuries/complications/*physiopathology MH - Symporters/genetics/*physiology MH - TRPV Cation Channels/antagonists & inhibitors/physiology MH - gamma-Aminobutyric Acid/physiology MH - K Cl- Cotransporters EDAT- 2010/06/12 06:00 MHDA- 2010/07/08 06:00 CRDT- 2010/06/12 06:00 PHST- 2010/06/12 06:00 [entrez] PHST- 2010/06/12 06:00 [pubmed] PHST- 2010/07/08 06:00 [medline] AID - NYAS5462 [pii] AID - 10.1111/j.1749-6632.2010.05462.x [doi] PST - ppublish SO - Ann N Y Acad Sci. 2010 Jun;1198:168-72. doi: 10.1111/j.1749-6632.2010.05462.x.