{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:29:29Z","timestamp":1792132169475,"version":"4.4.0"},"reference-count":31,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Aims:<\/jats:italic>\n                    <\/jats:bold>\n                    Impairment in adenosine monophosphate-activated protein kinase (AMPK) activity and NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation are associated with several metabolic and inflammatory diseases. In this study, we investigated the role of AMPK\/NLRP3 inflammasome axis in the molecular mechanism underlying pain perception.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Results:<\/jats:italic>\n                    <\/jats:bold>\n                    Impairment in AMPK activation induced by compound C or sunitinib, two AMPK inhibitors, provoked hyperalgesia in mice (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt;0.001) associated with marked NLRP3 inflammasome protein activation and increased serum levels of interleukin-1\u03b2 (IL-1\u03b2) (24.56\u00b10.82\u2009pg\/ml) and IL-18 (23.83\u00b11.882\u2009pg\/ml) compared with vehicle groups (IL-1\u03b2: 8.15\u00b10.44; IL-18: 4.92\u00b10.4). This effect was rescued by increasing AMPK phosphorylation\n                    <jats:italic toggle=\"yes\">via<\/jats:italic>\n                    metformin treatment (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt;0.001), caloric restriction diet (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt;0.001), or NLRP3 inflammasome genetic inactivation using NLRP3 knockout (nlrp3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    &lt;0.001). Deficient AMPK activation and overactivation of NLRP3 inflammasome axis were also observed in blood cells from patients with fibromyalgia (FM), a prevalent human chronic pain disease. In addition, metformin treatment (200\u2009mg\/daily), which increased AMPK activation, restored all biochemical alterations examined by us in blood cells and significantly improved clinical symptoms, such as, pain, fatigue, depression, disturbed sleep, and tender points, in patients with FM.\n                    <jats:bold>\n                      <jats:italic toggle=\"yes\">Innovation and Conclusions:<\/jats:italic>\n                    <\/jats:bold>\n                    These data suggest that AMPK\/NLRP3 inflammasome axis participates in chronic pain and that NLRP3 inflammasome inhibition by AMPK modulation may be a novel therapeutic target to fight against chronic pain and inflammatory diseases as FM.\n                    <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                    24, 157\u2013170.\n                  <\/jats:p>","DOI":"10.1089\/ars.2014.6120","type":"journal-article","created":{"date-parts":[[2015,7,1]],"date-time":"2015-07-01T13:45:38Z","timestamp":1435758338000},"page":"157-170","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":102,"title":["AMPK Phosphorylation Modulates Pain by Activation of NLRP3 Inflammasome"],"prefix":"10.1177","volume":"24","author":[{"given":"Pedro","family":"Bull\u00f3n","sequence":"first","affiliation":[{"name":"Universidad de Sevilla","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El\u00edsabet","family":"Alcocer-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Universidad de Sevilla","place":["Spain"]},{"name":"Universidad Pablo de Olavide-CSIC-Junta de Andaluc\u00eda and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel M.","family":"Carri\u00f3n","sequence":"additional","affiliation":[{"name":"Universidad Pablo de Olavide de Sevilla","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Mar\u00edn-Aguilar","sequence":"additional","affiliation":[{"name":"Universidad de Sevilla","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Garrido-Maraver","sequence":"additional","affiliation":[{"name":"Universidad Pablo de Olavide-CSIC-Junta de Andaluc\u00eda and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Rom\u00e1n-Malo","sequence":"additional","affiliation":[{"name":"Universidad de Sevilla","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus","family":"Ruiz-Cabello","sequence":"additional","affiliation":[{"name":"Centro Nacional de Investigaciones Cardiovasculares, and Universidad Complutense Madrid","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ognjen","family":"Culic","sequence":"additional","affiliation":[{"name":"University of Zagreb","place":["Croatia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Ryffel","sequence":"additional","affiliation":[{"name":"University and CNRS","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Apetoh","sequence":"additional","affiliation":[{"name":"INSERM","place":["France"]},{"name":"Centre Georges Fran\u00e7ois Leclerc","place":["France"]},{"name":"Universit\u00e9 de Bourgogne","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Ghiringhelli","sequence":"additional","affiliation":[{"name":"INSERM","place":["France"]},{"name":"Centre Georges Fran\u00e7ois Leclerc","place":["France"]},{"name":"Universit\u00e9 de Bourgogne","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Battino","sequence":"additional","affiliation":[{"name":"Universit\u00e0 Politecnica delle Marche","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio","family":"S\u00e1nchez-Alcazar","sequence":"additional","affiliation":[{"name":"Universidad Pablo de Olavide-CSIC-Junta de Andaluc\u00eda and Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario D.","family":"Cordero","sequence":"additional","affiliation":[{"name":"Universidad de Sevilla","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,1,20]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-003-0427-8"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2919"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2008.06.012"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20090613"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2013.5198"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar2918"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-35-11120.2003"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2008.04.005"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1532-2149.2013.00284.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3311"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2231"},{"key":"e_1_3_3_13_2","first-page":"517","article-title":"A 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A successful case of pain management using metformin in a patient with adiposis dolorosa. 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