title: Expression changes of cation chloride cotransporters in the rat spinal cord following intraplantar formalin.
abstract: Cation chloride cotransporters, K(+)-Cl(-) cotransporter 2 (KCC2) and Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1) are reported to be expressed in the neurons in the spinal cord and regulate intracellular Cl(-) concentration. Evidence has been accumulating that the expression of cation chloride cotransporters changes in inflammatory or neuropathic pain, and such changes take a part in pathophysiology of the persistent pain states. However, it is largely unknown how these cotransporters contribute to hyperalgesia in the acute pain state. We, therefore, investigated expression changes of KCC2 and NKCC1 in the spinal dorsal horn of the rat after the intraplantar injection of formalin as an acute nociceptive stimulus. The rats showed two phases (phases 1 and 2) of increase in pain-related behavior in response to formalin. We found that expression of KCC2-like immunoreactivity (IR) was reduced in lamina I and II in the lumbar spinal cord on the stimulated side in phase 1, and then recovered gradually. In contrast, the number of NKCC1-like IR-positive cells was unchanged over the period examined. These results suggest that KCC2, rather than NKCC1, mainly contributes to modulating excitability of the dorsal spinal cord neurons in the initial stage of formalin-evoked hyperalgesia.
authors.affiliation: Anesthesiology and Clinical Physiology, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Tokyo, Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Nomura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sakai
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Nagano
authors.forename: Masahiro
authors.initials: M
authors.lastname: Umino
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005528:Foot; D005557:Formaldehyde / Q000008:administration & dosage; D006930:Hyperalgesia / Q000139:chemically induced / Q000523:psychology; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007267:Injections; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000523:psychology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D028021:Sodium-Potassium-Chloride Symporters / Q000096:biosynthesis*; D064506:Solute Carrier Family 12, Member 2; D013116:Spinal Cord / Q000378:metabolism*; D013268:Stimulation, Chemical; D027981:Symporters / Q000096:biosynthesis*; D000096922:K Cl- Cotransporters
chemical_list: D005557:Formaldehyde; D012333:RNA, Messenger; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters; D000096922:K Cl- Cotransporters; C578879:Slc12a2 protein, rat