{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T13:09:13Z","timestamp":1759496953974,"version":"3.44.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>The dorsal reticular nucleus is a pain facilitatory area involved in diffuse noxious inhibitory control (DNIC) through opioidergic mechanisms that are poorly understood. The hypothesis was that signaling of \u03bc-opioid receptors is altered in this area with prolonged chronic inflammatory pain and that this accounts for the loss of DNICs occurring in this condition.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Monoarthritis was induced in male Wistar rats (n = 5 to 9\/group) by tibiotarsal injection of complete Freund\u2019s adjuvant. The immunolabeling of \u00b5-opioid receptors and the phosphorylated forms of \u00b5-opioid receptors and cAMP response element binding protein was quantified. Pharmacologic manipulation of \u03bc-opioid receptors at the dorsal reticular nucleus was assessed in DNIC using the Randall\u2013Selitto test.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>At 42 days of monoarthritis, \u03bc-opioid receptor labeling decreased at the dorsal reticular nucleus, while its phosphorylated form and the phosphorylated cAMP response element binding protein increased. [<jats:sc>d<\/jats:sc>-Ala<jats:sup>2<\/jats:sup>, <jats:italic toggle=\"yes\">N<\/jats:italic>-Me-Phe<jats:sup>4<\/jats:sup>, Gly<jats:sup>5<\/jats:sup>-ol]-enkephalin acetate (DAMGO) enhanced DNIC analgesia in normal animals (means \u00b1 SD: pre-DNIC: 126.9\u2009\u00b1\u20097.0\u2009g; DNIC \u2212 DAMGO: 147.5\u2009\u00b1\u20098.0\u2009g <jats:italic toggle=\"yes\">vs<\/jats:italic>. DNIC + DAMGO: 198.1\u2009\u00b1\u200919.3\u2009g; <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.001), whereas it produced hyperalgesia in monoarthritis (pre-DNIC: 67.8\u2009\u00b1\u20097.5\u2009g; DNIC \u2212 DAMGO: 70.6\u2009\u00b1\u20097.7\u2009g <jats:italic toggle=\"yes\">vs<\/jats:italic>. DNIC + DAMGO: 32.2\u2009\u00b1\u20092.6\u2009g; <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.001). An ultra-low dose of naloxone, which prevents the excitatory signaling of the \u03bc-opioid receptor, restored DNIC analgesia in monoarthritis (DNIC \u2212 naloxone: 60.0\u2009\u00b1\u20096.1\u2009g <jats:italic toggle=\"yes\">vs<\/jats:italic>. DNIC + naloxone: 98.0\u2009\u00b1\u200913.5\u2009g; <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.001), compared to saline (DNIC \u2212 saline: 62.5\u2009\u00b1\u20095.2\u2009g <jats:italic toggle=\"yes\">vs<\/jats:italic>. DNIC + saline: 64.2\u2009\u00b1\u20093.8\u2009g). When injected before DAMGO, it restored DNIC analgesia and decreased the phosphorylated cAMP response element binding protein in monoarthritis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The dorsal reticular nucleus is likely involved in a facilitatory pathway responsible for DNIC hyperalgesia. The shift of \u03bc-opioid receptor signaling to excitatory in this pathway likely accounts for the loss of DNIC analgesia in monoarthritis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Editor\u2019s Perspective<\/jats:title>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>What We Already Know about This Topic<\/jats:title>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>What This Article Tells Us That Is New<\/jats:title>\n          <\/jats:sec>","DOI":"10.1097\/aln.0000000000004956","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T15:14:06Z","timestamp":1708528446000},"page":"1176-1191","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":5,"title":["\u03bc-Opioid Receptor Activation at the Dorsal Reticular Nucleus Shifts Diffuse Noxious Inhibitory Controls to Hyperalgesia in Chronic Joint Pain in Male Rats"],"prefix":"10.1097","volume":"140","author":[{"given":"Raquel","family":"Pereira-Silva","sequence":"first","affiliation":[{"name":"Institute for Research and Innovation in Health (i3S) of the University of Porto, Porto, Portugal; Institute for Molecular and Cell Biology (IBMC), University of Porto, Porto, Portugal; Department of Biomedicine - Unit of Experimental Biology, Faculty of Medicine, University of Porto, Porto, Portugal."}]},{"given":"Armando","family":"Teixeira-Pinto","sequence":"additional","affiliation":[{"name":"Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia; Centre for Kidney Research, Kids Research Institute, Children\u2019s Hospital at Westmead, Sydney, New South Wales, Australia."}]},{"given":"Fani L.","family":"Neto","sequence":"additional","affiliation":[{"name":"Institute for Research and Innovation in Health (i3S) of the University of Porto, Porto, Portugal; Institute for Molecular and Cell Biology (IBMC), University of Porto, Porto, Portugal; Department of Biomedicine - Unit of Experimental Biology, Faculty of Medicine, University of Porto, Porto, Portugal."}]},{"given":"Isabel","family":"Martins","sequence":"additional","affiliation":[{"name":"Institute for Research and Innovation in Health (i3S) of the University of Porto, Porto, Portugal; Institute for Molecular and Cell Biology (IBMC), University of Porto, Porto, Portugal; Department of Biomedicine - Unit of Experimental Biology, Faculty of Medicine, University of Porto, Porto, Portugal."}]}],"member":"276","published-online":{"date-parts":[[2024,2,21]]},"reference":[{"key":"R1-20250817","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/SPC.0000000000000126","article-title":"Conditioned pain modulation.","volume":"9","author":"Nir","year":"2015","journal-title":"Curr Opin Support Palliat 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