{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T03:33:12Z","timestamp":1790911992882,"version":"4.1.0"},"reference-count":39,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2007,1,1]],"date-time":"2007-01-01T00:00:00Z","timestamp":1167609600000},"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":[[2007,1,1]]},"abstract":"<jats:sec><jats:title>Background:<\/jats:title><jats:p> The Na<jats:sup>+<\/jats:sup>, K<jats:sup>+<\/jats:sup>, 2Cl<jats:sup>\u2212<\/jats:sup> type I cotransporter (NKCC1) and TRPV1 receptors, at the level of the dorsal horn, have been implicated in mediating allodynia in response to an inflammatory insult. The NKCC1 cotransporter regulates intracellular [Cl<jats:sup>\u2212<\/jats:sup>] and thus the magnitude and polarity of GABA<jats:sub>A<\/jats:sub> receptor responses in neurons. TRPV1 receptors transduce diverse chemical and natural stimuli in nociceptors and are critical for inflammatory hyperalgesia. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p> Here we have tested the role of spinal NKCC1 cotransporters and TRPV1 receptors in referred allodynia in a model of visceral hyperalgesia in mice. Intrathecal (IT) injection of the NKCC1 inhibitor bumetanide (BUM, 1 nmol) inhibited referred, abdominal allodynia evoked by an intracolonic capsaicin injection. BUM was effective when injected IT either before or up to 4 hrs after the establishment of referred allodynia. The TRPV1 antagonist AMG 9810 (1 nmol) also inhibited referred allodynia in this model suggesting the involvement of an endogenous TRPV1 agonist in the dorsal horn in referred allodynia. In support of this suggestion, the endovanilloid TRPV1 agonist, narachidonoyl- dopamine (NADA, 1 or 10 nmol, IT) evoked stroking allodynia in the hindpaw that was blocked by co-treatment with AMG 9810 (1 nmol). The TRPV1-dependent stroking allodynia caused by NADA appeared to be functionally linked to NKCC1 because BUM (1 nmol) also inhibited NADA-evoked stroking allodynia. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p> Our findings indicate that spinal NKCC1 and TRPV1 are critical for referred allodynia mediated by a painful visceral stimulus. Moreover, they suggest that endogenous TRPV1 agonists, released in the CNS in painful conditions, might stimulate TRPV1 receptors on primary afferents that, in turn, play a role in increasing NKCC1 activity leading to allodynia. <\/jats:p><\/jats:sec>","DOI":"10.1186\/1744-8069-3-17","type":"journal-article","created":{"date-parts":[[2007,6,30]],"date-time":"2007-06-30T06:13:47Z","timestamp":1183184027000},"source":"Crossref","is-referenced-by-count":47,"title":["Spinal NKCC1 Blockade Inhibits TRPV1-Dependent Referred Allodynia"],"prefix":"10.1177","volume":"3","author":[{"given":"Mark H","family":"Pitcher","sequence":"first","affiliation":[{"name":"McGill University, Anesthesia Research Unit, Faculty of Medicine, Faculty of Dentistry and McGill Centre for Research on Pain, 3655 Sir William Osler, McIntyre Medical Bldg 1207, Montreal, QC, H3G 1Y6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore J","family":"Price","sequence":"additional","affiliation":[{"name":"McGill University, Anesthesia Research Unit, Faculty of Medicine, Faculty of Dentistry and McGill Centre for Research on Pain, 3655 Sir William Osler, McIntyre Medical Bldg 1207, Montreal, QC, H3G 1Y6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose M","family":"Entrena","sequence":"additional","affiliation":[{"name":"University of Granada Faculty of Medicine, Department of Pharmacology and Neurosciences Institute, Avenida de Madrid 12, E-18012, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Cervero","sequence":"additional","affiliation":[{"name":"McGill University, Anesthesia Research Unit, Faculty of Medicine, Faculty of Dentistry and McGill Centre for Research on Pain, 3655 Sir William Osler, McIntyre Medical Bldg 1207, Montreal, QC, H3G 1Y6, 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