{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T00:32:05Z","timestamp":1793665925529,"version":"4.5.1"},"reference-count":33,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2008,1,1]],"date-time":"2008-01-01T00:00:00Z","timestamp":1199145600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mol Pain"],"published-print":{"date-parts":[[2008,1,1]]},"abstract":"<jats:sec><jats:title>Background:<\/jats:title><jats:p> Altered Cl<jats:sup>\u2212<\/jats:sup> homeostasis and GABAergic function are associated with nociceptive input hypersensitivity. This study investigated the role of two major intracellular Cl<jats:sup>\u2212<\/jats:sup> regulatory proteins, Na<jats:sup>+<\/jats:sup>-K<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup> cotransporter 1 (NKCC1) and K<jats:sup>+<\/jats:sup>-Cl<jats:sup>\u2212<\/jats:sup> cotransporter 2 (KCC2), in neuropathic pain following spinal cord injury (SCI). <\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p> Sprague-Dawley rats underwent a contusive SCI at T9 using the MASCIS impactor. The rats developed hyperalgesia between days 21 and 42 post-SCI. Thermal hyperalgesia (TH) was determined by a decrease in hindpaw thermal withdrawal latency time (WLT) between days 21 and 42 post-SCI. Rats with TH were then treated with either vehicle (saline containing 0.25% NaOH) or NKCC1 inhibitor bumetanide (BU, 30 mg\/kg, i.p.) in vehicle. TH was then re-measured at 1 h post-injection. Administration of BU significantly increased the mean WLT in rats (p &lt; 0.05). The group administered with the vehicle alone showed no anti-hyperalgesic effects. Moreover, an increase in NKCC1 protein expression occurred in the lesion epicenter of the spinal cord during day 2\u201314 post-SCI and peaked on day 14 post-SCI (p &lt; 0.05). Concurrently, a down-regulation of KCC2 protein was detected during day 2\u201314 post-SCI. The rats with TH exhibited a sustained loss of KCC2 protein during post-SCI days 21\u201342. No significant changes of these proteins were detected in the rostral region of the spinal cord. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p> Taken together, expression of NKCC1 and KCC2 proteins was differentially altered following SCI. The anti-hyperalgesic effect of NKCC1 inhibition suggests that normal or elevated NKCC1 function and loss of KCC2 function play a role in the development and maintenance of SCI-induced neuropathic pain. <\/jats:p><\/jats:sec>","DOI":"10.1186\/1744-8069-4-36","type":"journal-article","created":{"date-parts":[[2012,5,8]],"date-time":"2012-05-08T15:09:29Z","timestamp":1336489769000},"source":"Crossref","is-referenced-by-count":107,"title":["The Role of Cation-Dependent Chloride Transporters in Neuropathic Pain Following Spinal Cord Injury"],"prefix":"10.1177","volume":"4","author":[{"given":"Samuel W","family":"Cramer","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Baggott","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Cain","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Tilghman","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Allcock","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurwattan","family":"Miranpuri","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharad","family":"Rajpal","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Resnick","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2008,1,1]]},"reference":[{"key":"bibr1-1744-8069-4-36","doi-asserted-by":"publisher","DOI":"10.1159\/000087657"},{"key":"bibr2-1744-8069-4-36","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(87)90098-4"},{"key":"bibr3-1744-8069-4-36","doi-asserted-by":"publisher","DOI":"10.2174\/1568026054367629"},{"key":"bibr4-1744-8069-4-36","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2007.09.003"},{"key":"bibr5-1744-8069-4-36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2006.05.013"},{"key":"bibr6-1744-8069-4-36","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3959(03)00250-1"},{"key":"bibr7-1744-8069-4-36","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(01)00091-4"},{"key":"bibr8-1744-8069-4-36","doi-asserted-by":"publisher","DOI":"10.1038\/nrn920"},{"key":"bibr9-1744-8069-4-36","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-16-05962.2001"},{"key":"bibr10-1744-8069-4-36","doi-asserted-by":"publisher","DOI":"10.1126\/science.2424084"},{"key":"bibr11-1744-8069-4-36","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-20-07531.2000"},{"key":"bibr12-1744-8069-4-36","doi-asserted-by":"crossref","unstructured":"Miletic G, Miletic V: Loose ligation of the sciatic nerve is associated with TrkB receptor-dependent decreases in KCC2 protein levels in the ipsilateral spinal dorsal horn. 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