{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T06:36:50Z","timestamp":1772692610979,"version":"3.50.1"},"reference-count":67,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":2646,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2001,11]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Magnesium (Mg)\u2010deficient rats develop a mechanical hyperalgesia which is reversed by a N\u2010Methyl\u2010<jats:sc>D<\/jats:sc>\u2010Aspartate (NMDA) receptor antagonist. Given that functioning of this receptor\u2010channel is modulated by Mg, we wondered whether facilitated activation of NMDA receptors in Mg deficiency state may in turn trigger a cascade of specific intracellular events present in persistent pain. Hence, we tested several antagonists of NMDA and non\u2010NMDA receptors as well as compounds interfering with the functioning of intracellular second messengers for effects on hyperalgesia in Mg\u2010deficient rats.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Hyperalgesic Mg\u2010deficient rats were administered intrathecally (10\u2003\u03bcl) or intraperitoneally with different antagonists. After drug injection, pain sensitivity was evaluated by assessing the vocalization threshold in response to a mechanical stimulus (paw pressure test) over 2\u2003h.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Intrathecal administration of MgSO<jats:sub>4<\/jats:sub> (1.6, 3.2, 4.8, 6.6\u2003\u03bcmol) as well as NMDA receptor antagonists such as MK\u2010801 (0.6, 6.0, 60\u2003nmol), AP\u20105 (10.2, 40.6, 162.3\u2003nmol) and DCKA (0.97, 9.7, 97\u2003nmol) dose\u2010dependently reversed the hyperalgesia. Chelerythrine chloride, a protein kinase C (PKC) inhibitor (1, 10.4, 104.2\u2003nmol) and 7\u2010NI, a specific nitric oxide (NO) synthase inhibitor (37.5, 75, 150\u2003\u03bcmol\u2003kg<jats:sup>\u22121<\/jats:sup>, i.p.) induced an anti\u2010hyperalgesic effect in a dose\u2010dependent manner. SR\u2010140333 (0.15, 1.5, 15\u2003nmol) and SR\u201048968 (0.17, 1.7, 17\u2003nmol), antagonists of neurokinin receptors, produced a significant, but moderate, increase in vocalization threshold.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These results demonstrate that Mg\u2010deficiency induces a sensitization of nociceptive pathways in the spinal cord which involves NMDA and non\u2010NMDA receptors. Furthermore, the data is consistent with an active role of PKC, NO and, to a lesser extent substance P in the intracellular mechanisms leading to hyperalgesia.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2001) <jats:bold>134<\/jats:bold>, 1227\u20131236; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0704354\">10.1038\/sj.bjp.0704354<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0704354","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T21:35:16Z","timestamp":1106948116000},"page":"1227-1236","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Role of spinal NMDA receptors, protein kinase C and nitric oxide synthase in the hyperalgesia induced by magnesium deficiency in rats"],"prefix":"10.1111","volume":"134","author":[{"given":"Sophie","family":"Begon","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gis\u00e8le","family":"Pickering","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Eschalier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Mazur","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yves","family":"Rayssiguier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claude","family":"Dubray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1993.tb13796.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)03028-6"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(88)90163-X"},{"key":"e_1_2_7_5_1","first-page":"829","article-title":"Efficacy of spinal NMDA receptor antagonism in formalin hyperalgesia and nerve evoked allodynia in the rat","volume":"280","author":"CHAPLAN S.R.","year":"1997","journal-title":"JPET"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.18.10.963"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02769177"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(91)90339-U"},{"key":"e_1_2_7_9_1","doi-asserted-by":"crossref","first-page":"3665","DOI":"10.1523\/JNEUROSCI.12-09-03665.1992","article-title":"The contribution of excitatory amino acids to central sensitization and persistent nociception after formalin\u2010induced tissue injury","volume":"12","author":"CODERRE T.J.","year":"1992","journal-title":"J. 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