{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T08:48:16Z","timestamp":1768898896695,"version":"3.49.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Increased descending pain facilitation accounts for opioid-induced hyperalgesia, but the underlying mechanisms remain elusive. Given the role of \u00b5-opioid receptors in opioid-induced hyperalgesia in animals, the authors hypothesized that the dorsal reticular nucleus, a medullary pain facilitatory area, is involved in opioid-induced hyperalgesia through altered \u00b5-opioid receptor signaling.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>The authors used male Wistar rats (n = 5 to 8 per group), chronically infused with morphine, to evaluate in the dorsal reticular nucleus the expressions of the \u00b5-opioid receptor and phosphorylated cAMP response element-binding, a downstream marker of excitatory \u00b5-opioid receptor signaling. The authors used pharmacologic and gene-mediated approaches. Nociceptive behaviors were evaluated by the von Frey and hot-plates tests.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Lidocaine fully reversed mechanical and thermal hypersensitivity induced by chronic morphine. Morphine-infusion increased \u00b5-opioid receptor, without concomitant messenger RNA changes, and phosphorylated cAMP response element-binding levels at the dorsal reticular nucleus. \u00b5-opioid receptor knockdown in morphine-infused animals attenuated the decrease of mechanical thresholds and heat-evoked withdrawal latencies compared with the control vector (von Frey [mean \u00b1 SD]: \u221217 \u00b1 8% <jats:italic toggle=\"yes\">vs.<\/jats:italic> \u221240 \u00b1 9.0%; <jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.001; hot-plate: \u221210 \u00b1 5% <jats:italic toggle=\"yes\">vs.<\/jats:italic> \u221232 \u00b1 10%; <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.001). \u00b5-opioid receptor knockdown in control animals induced the opposite (von Frey: \u221231 \u00b1 8% <jats:italic toggle=\"yes\">vs.<\/jats:italic> \u221217 \u00b1 8%; <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.053; hotplate: \u221224 \u00b1 6% <jats:italic toggle=\"yes\">vs.<\/jats:italic> \u22123 \u00b1 10%; <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.001). The \u00b5-opioid receptor agonist (D-ALA2,N-ME-PHE4,GLY5-OL)-enkephalin acetate (DAMGO) decreased mechanical thresholds and did not affect heat-evoked withdrawal latencies in morphine-infused animals. In control animals, DAMGO increased both mechanical thresholds and heat-evoked withdrawal latencies. Ultra-low-dose naloxone, which prevents the excitatory signaling of the \u00b5-opioid receptor, administered alone, attenuated mechanical and thermal hypersensitivities, and coadministered with DAMGO, restored DAMGO analgesic effects and decreased phosphorylated cAMP response element-binding levels.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Chronic morphine shifted \u00b5-opioid receptor signaling from inhibitory to excitatory at the dorsal reticular nucleus, likely enhancing descending facilitation during opioid-induced hyperalgesia in the rat.<\/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.0000000000003412","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T10:00:00Z","timestamp":1592820000000},"page":"628-644","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":14,"title":["Shift of \u00b5-opioid Receptor Signaling in the Dorsal Reticular Nucleus Is Implicated in Morphine-induced Hyperalgesia in Male Rats"],"prefix":"10.1097","volume":"133","author":[{"given":"Ana Rita","family":"Costa","sequence":"first","affiliation":[]},{"given":"Mar\u00edlia","family":"Sousa","sequence":"additional","affiliation":[]},{"given":"Steven P.","family":"Wilson","sequence":"additional","affiliation":[]},{"given":"Carlos","family":"Reguenga","sequence":"additional","affiliation":[]},{"given":"Armando","family":"Teixeira-Pinto","sequence":"additional","affiliation":[]},{"given":"Isaura","family":"Tavares","sequence":"additional","affiliation":[]},{"given":"Isabel","family":"Martins","sequence":"additional","affiliation":[]}],"member":"276","published-online":{"date-parts":[[2020,6,17]]},"reference":[{"key":"R1-20241226","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1037\/a0013628","article-title":"Opioids and the treatment of chronic pain: controversies, current status, and future directions.","volume":"16","author":"Rosenblum","year":"2008","journal-title":"Exp Clin Psychopharmacol."},{"key":"R2-20241226","doi-asserted-by":"crossref","first-page":"145","DOI":"10.36076\/ppj.2011\/14\/145","article-title":"A comprehensive review of opioid-induced hyperalgesia.","volume":"14","author":"Lee","year":"2011","journal-title":"Pain Physician."},{"key":"R3-20241226","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1016\/S0140-6736(19)30430-1","article-title":"Perioperative opioid analgesia-when is enough too much? 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