{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:49:28Z","timestamp":1788922168380,"version":"build-2803163510"},"reference-count":106,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas","doi-asserted-by":"publisher","award":["A1-S-40015"],"award-info":[{"award-number":["A1-S-40015"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004771","name":"Escuela Superior de Ingenier\u00eda Mec\u00e1nica y El\u00e9ctrica, Instituto Polit\u00e9cnico Nacional","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004771","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.ejphar.2025.178026","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T15:02:16Z","timestamp":1753974136000},"page":"178026","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Activation of spinal melatonin MT2 receptors reduces neuropathic pain in mice in a sex-dependent manner"],"prefix":"10.1016","volume":"1004","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8228-1314","authenticated-orcid":false,"given":"Crystell G.","family":"Guzm\u00e1n-Priego","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itzel I.","family":"Ramos-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan M.","family":"Piza\u00f1a-Encarnaci\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M.","family":"Islas-Espinoza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5453-8312","authenticated-orcid":false,"given":"Mar\u00eda J.","family":"Escoto-Rosales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana K.","family":"Morales-Galindo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myrna","family":"D\u00e9ciga-Campos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick J.","family":"Rodr\u00edguez-Palma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1038-8400","authenticated-orcid":false,"given":"Vinicio","family":"Granados-Soto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"7","key":"10.1016\/j.ejphar.2025.178026_bib1","first-page":"236","article-title":"Melatonin synergizes with the antinociceptive effect of N-palmitoylethanolamide and paracetamol","volume":"77","author":"Alavez-P\u00e9rez","year":"2022","journal-title":"Pharmazie"},{"issue":"743","key":"10.1016\/j.ejphar.2025.178026_bib2","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.adg3036","article-title":"Nociceptor spontaneous activity is responsible for fragmenting non-rapid eye movement sleep in mouse models of neuropathic pain","volume":"16","author":"Alexandre","year":"2024","journal-title":"Sci. Transl. Med."},{"issue":"6","key":"10.1016\/j.ejphar.2025.178026_bib3","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3892\/etm.2020.9294","article-title":"Impairment in locomotor activity as an objective measure of pain and analgesia in a rat model of osteoarthritis","volume":"20","author":"Alsalem","year":"2020","journal-title":"Exp. Ther. Med."},{"issue":"3","key":"10.1016\/j.ejphar.2025.178026_bib4","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.pain.2007.01.025","article-title":"Oral and spinal melatonin reduces tactile allodynia in rats via activation of MT2 and opioid receptors","volume":"132","author":"Ambriz-Tututi","year":"2007","journal-title":"Pain"},{"issue":"15\u201316","key":"10.1016\/j.ejphar.2025.178026_bib5","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.lfs.2009.01.024","article-title":"Melatonin: a hormone that modulates pain","volume":"84","author":"Ambriz-Tututi","year":"2009","journal-title":"Life Sci."},{"issue":"1","key":"10.1016\/j.ejphar.2025.178026_bib6","doi-asserted-by":"crossref","DOI":"10.1111\/bcpt.14120","article-title":"Preclinical evidence for a drug-drug interaction between cannabinol and melatonin","volume":"136","author":"Anderson","year":"2025","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"issue":"1","key":"10.1016\/j.ejphar.2025.178026_bib7","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.smrv.2004.05.002","article-title":"Melatonin as a chronobiotic","volume":"9","author":"Arendt","year":"2005","journal-title":"Sleep Med. Rev."},{"issue":"1\u20133","key":"10.1016\/j.ejphar.2025.178026_bib8","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ejphar.2007.09.006","article-title":"Melatonin reduces formalin-induced nociception and tactile allodynia in diabetic rats","volume":"577","author":"Arreola-Espino","year":"2007","journal-title":"Eur. J. Pharmacol."},{"issue":"6","key":"10.1016\/j.ejphar.2025.178026_bib9","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s00210-003-0751-2","article-title":"New selective ligands of human cloned melatonin MT1 and MT2 receptors","volume":"367","author":"Audinot","year":"2003","journal-title":"Naunyn-Schmiedebergs Arch Pharmacol"},{"key":"10.1016\/j.ejphar.2025.178026_bib10","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2024.176386","article-title":"Sex differences in carbamazepine effects in a rat model of trigeminal neuropathic pain","volume":"967","author":"Baggio","year":"2024","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2025.178026_bib11","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1097\/j.pain.0000000000001387","article-title":"Activation of the integrated stress response in nociceptors drives methylglyoxal-induced pain","volume":"160","author":"Barrag\u00e1n-Iglesias","year":"2019","journal-title":"Pain"},{"issue":"2","key":"10.1016\/j.ejphar.2025.178026_bib12","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1007\/s002130100821","article-title":"Importance of sex and relative efficacy at the mu opioid receptor in the development of tolerance and cross-tolerance to the antinociceptive effects of opioids","volume":"158","author":"Barrett","year":"2001","journal-title":"Psychopharmacology (Berl)"},{"issue":"3","key":"10.1016\/j.ejphar.2025.178026_bib13","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/ng.1053","article-title":"Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes","volume":"44","author":"Bonnefond","year":"2012","journal-title":"Nat. Genet."},{"issue":"1\u20132","key":"10.1016\/j.ejphar.2025.178026_bib14","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/S0014-2999(00)00491-X","article-title":"Sex differences in forced-swim and open-field test behaviours after chronic administration of melatonin","volume":"402","author":"Brotto","year":"2000","journal-title":"Eur. J. Pharmacol."},{"issue":"1","key":"10.1016\/j.ejphar.2025.178026_bib15","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0165-0270(94)90144-9","article-title":"Quantitative assessment of tactile allodynia in the rat paw","volume":"53","author":"Chaplan","year":"1994","journal-title":"J. Neurosci. Methods"},{"issue":"2","key":"10.1016\/j.ejphar.2025.178026_bib16","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/jpi.12029","article-title":"Melatonin reduces median nerve injury-induced mechanical hypersensitivity via inhibition of microglial p38 mitogen-activated protein kinase activation in rat cuneate nucleus","volume":"54","author":"Chiang","year":"2013","journal-title":"J. Pineal Res."},{"issue":"5","key":"10.1016\/j.ejphar.2025.178026_bib17","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.ejpain.2004.01.003","article-title":"Sex differences in pain and analgesia: the role of gonadal hormones","volume":"8","author":"Craft","year":"2004","journal-title":"Eur. J. Pain"},{"key":"10.1016\/j.ejphar.2025.178026_bib18","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1600-079X.1997.tb00342.x","article-title":"Protective effect of melatonin in carrageenan-induced models of local inflammation: relationship to its inhibitory effect on nitric oxide production and its peroxynitrite scavenging activity","volume":"23","author":"Cuzzocrea","year":"1997","journal-title":"J. Pineal Res."},{"key":"10.1016\/j.ejphar.2025.178026_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2023.175696","article-title":"Spinal dopaminergic D1-and D2-like receptors have a sex-dependent effect in an experimental model of fibromyalgia","volume":"948","author":"De la Luz-Cuellar","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2025.178026_bib20","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2019.172443","article-title":"Blockade of spinal \u03b15-GABAA receptors differentially reduces reserpine-induced fibromyalgia-type pain in female rats","volume":"858","author":"De la Luz-Cuellar","year":"2019","journal-title":"Eur. J. Pharmacol."},{"issue":"1","key":"10.1016\/j.ejphar.2025.178026_bib21","doi-asserted-by":"crossref","first-page":"8472","DOI":"10.1038\/s41598-022-12248-8","article-title":"Behavioral and inflammatory sex differences revealed by celecoxib nanotherapeutic treatment of peripheral neuroinflammation","volume":"12","author":"Deal","year":"2022","journal-title":"Sci. Rep."},{"issue":"7","key":"10.1016\/j.ejphar.2025.178026_bib23","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1021\/jm0255872","article-title":"Design and synthesis of naphthalenic dimers as selective MT1 melatoninergic ligands","volume":"46","author":"Descamps-Fran\u00e7ois","year":"2003","journal-title":"J. Med. Chem."},{"issue":"2","key":"10.1016\/j.ejphar.2025.178026_bib24","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0165-0270(97)00097-6","article-title":"Characterization of variables defining hindpaw withdrawal latency evoked by radiant thermal stimuli","volume":"76","author":"Dirig","year":"1997","journal-title":"J. Neurosci. Methods"},{"issue":"1","key":"10.1016\/j.ejphar.2025.178026_bib25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0014-2999(99)00701-3","article-title":"Acute low doses of melatonin stimulate rat sex behavior: the role of serotonin neurotransmission","volume":"385","author":"Drago","year":"1999","journal-title":"Eur. J. Pharmacol."},{"issue":"3","key":"10.1016\/j.ejphar.2025.178026_bib26","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1124\/pr.110.002832","article-title":"International union of basic and clinical pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors","volume":"62","author":"Dubocovich","year":"2010","journal-title":"Pharmacol. Rev."},{"issue":"3","key":"10.1016\/j.ejphar.2025.178026_bib27","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/PL00004956","article-title":"Melatonin receptor antagonists that differentiate between the human Mel1a and Mel1b recombinant subtypes are used to assess the pharmacological profile of the rabbit retina ML1 presynaptic heteroreceptor","volume":"355","author":"Dubocovich","year":"1997","journal-title":"Naunyn-Schmiedebergs Arch Pharmacol"},{"issue":"12","key":"10.1016\/j.ejphar.2025.178026_bib28","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1096\/fasebj.12.12.1211","article-title":"Selective MT2 melatonin receptor antagonists block melatonin-mediated phase advances of circadian rhythms","volume":"12","author":"Dubocovich","year":"1998","journal-title":"FASEB J."},{"issue":"7","key":"10.1016\/j.ejphar.2025.178026_bib29","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1002\/jdn.10374","article-title":"Melatonin attenuates affective disorders and cognitive deficits induced by perinatal exposure to a glyphosate-based herbicide via antioxidant pathway in adult Male and female rats","volume":"84","author":"El Hamzaoui","year":"2024","journal-title":"Int. J. Dev. Neurosci."},{"issue":"7","key":"10.1016\/j.ejphar.2025.178026_bib30","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.3390\/ijms18071389","article-title":"Oral supplementation of melatonin protects against fibromyalgia-related skeletal muscle alterations in reserpine-induced myalgia rats","volume":"18","author":"Favero","year":"2017","journal-title":"Int. J. Mol. Sci."},{"issue":"6","key":"10.1016\/j.ejphar.2025.178026_bib31","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1111\/jnc.15140","article-title":"Sex-dependent pronociceptive role of spinal \u03b15-GABAA receptor and its epigenetic regulation in neuropathic rodents","volume":"156","author":"Franco-Enz\u00e1stiga","year":"2021","journal-title":"J. Neurochem."},{"issue":"4","key":"10.1016\/j.ejphar.2025.178026_bib32","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.jpain.2022.12.005","article-title":"Bestrophin-1 participates in neuropathic pain induced by spinal nerve transection but not spinal nerve ligation","volume":"24","author":"Garc\u00eda","year":"2023","journal-title":"J. Pain"},{"key":"10.1016\/j.ejphar.2025.178026_bib33","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.yhbeh.2017.10.011","article-title":"Sex differences and estradiol involvement in hyperalgesia and allodynia in an experimental model of fibromyalgia","volume":"97","author":"Hernandez-Leon","year":"2018","journal-title":"Horm. Behav."},{"issue":"1\u20133","key":"10.1016\/j.ejphar.2025.178026_bib34","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ejphar.2008.07.068","article-title":"Possible participation of the nitric oxide-cyclic GMP-protein kinase G-K+ channels pathway in the peripheral antinociception of melatonin","volume":"596","author":"Hern\u00e1ndez-Pacheco","year":"2008","journal-title":"Eur. J. Pharmacol."},{"issue":"4","key":"10.1016\/j.ejphar.2025.178026_bib35","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1002\/1097-0142(20000815)89:4<817::AID-CNCR14>3.0.CO;2-6","article-title":"ICI 182,780 (Faslodex): development of a novel, \"pure\" antiestrogen","volume":"89","author":"Howell","year":"2000","journal-title":"Cancer"},{"issue":"23","key":"10.1016\/j.ejphar.2025.178026_bib36","doi-asserted-by":"crossref","first-page":"4227","DOI":"10.1021\/acschemneuro.3c00616","article-title":"Melatonin relieves paclitaxel-induced neuropathic pain by regulating pNEK2-dependent epigenetic pathways in DRG neurons","volume":"14","author":"Hsieh","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"10.1016\/j.ejphar.2025.178026_bib37","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuint.2020.104827","article-title":"Melatonin reduces neuropathic pain behavior and glial activation through MT2 melatonin receptor modulation in a rat model of lysophosphatidylcholine-induced demyelination neuropathy","volume":"140","author":"Huang","year":"2020","journal-title":"Neurochem. Int."},{"key":"10.1016\/j.ejphar.2025.178026_bib38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.phrs.2018.10.027","article-title":"The antidiabetic drug metformin prevents and reverses neuropathic pain and spinal cord microglial activation in male but not female mice","volume":"139","author":"Inyang","year":"2019","journal-title":"Pharmacol. Res."},{"issue":"5","key":"10.1016\/j.ejphar.2025.178026_bib39","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/j.pain.2011.01.046","article-title":"Spinal estrogen receptor alpha mediates estradiol-induced pronociception in a visceral pain model in the rat","volume":"152","author":"Ji","year":"2011","journal-title":"Pain"},{"issue":"4","key":"10.1016\/j.ejphar.2025.178026_bib40","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1210\/en.2005-0648","article-title":"Sex-dependent effect of melatonin on systemic erythematosus lupus developed in Mrl\/Mpj-Faslpr mice: it ameliorates the disease course in females, whereas it exacerbates it in males","volume":"147","author":"Jimenez-Caliani","year":"2006","journal-title":"Endocrinology"},{"issue":"18","key":"10.1016\/j.ejphar.2025.178026_bib41","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1111\/bph.13536","article-title":"Update on melatonin receptors: IUPHAR review 20","volume":"173","author":"Jockers","year":"2016","journal-title":"Br. J. Pharmacol."},{"issue":"6","key":"10.1016\/j.ejphar.2025.178026_bib42","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1038\/bjp.2008.184","article-title":"Melatonin receptors, heterodimerization, signal transduction and binding sites: what's new?","volume":"154","author":"Jockers","year":"2008","journal-title":"Br. J. Pharmacol."},{"issue":"3","key":"10.1016\/j.ejphar.2025.178026_bib43","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1007\/s12035-016-9727-3","article-title":"Modulation of diabetes-induced oxidative stress, apoptosis, and Ca2+ entry through TRPM2 and TRPV1 channels in dorsal root ganglion and hippocampus of diabetic rats by melatonin and selenium","volume":"54","author":"Kahya","year":"2017","journal-title":"Mol. Neurobiol."},{"issue":"2","key":"10.1016\/j.ejphar.2025.178026_bib44","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.physbeh.2012.07.003","article-title":"Estrogen blocks the protective action of melatonin in a behavioral model of ethanol-induced hangover in mice","volume":"107","author":"Karadayian","year":"2012","journal-title":"Physiol. Behav."},{"issue":"1","key":"10.1016\/j.ejphar.2025.178026_bib45","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2174\/1567202612666150102151900","article-title":"Melatonin leads to axonal regeneration, reduction in oxidative stress, and improved functional recovery following sciatic nerve injury","volume":"12","author":"Kaya","year":"2015","journal-title":"Curr. Neurovascular Res."},{"key":"10.1016\/j.ejphar.2025.178026_bib47","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1744-8069-10-19","article-title":"Voltage-gated sodium channel expression in mouse DRG after SNI leads to re-evaluation of projections of injured fibers","volume":"10","author":"Laedermann","year":"2014","journal-title":"Mol. Pain"},{"key":"10.1016\/j.ejphar.2025.178026_bib48","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1016\/0024-3205(81)90710-4","article-title":"Involvement of the pineal gland and melatonin in murine analgesia","volume":"29","author":"Lakin","year":"1981","journal-title":"Life Sci."},{"issue":"4","key":"10.1016\/j.ejphar.2025.178026_bib49","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1111\/j.1476-5381.2008.00066.x","article-title":"Protopanaxadiol and protopanaxatriol bind to glucocorticoid and oestrogen receptors in endothelial cells","volume":"156","author":"Leung","year":"2009","journal-title":"Br. J. Pharmacol."},{"issue":"7","key":"10.1016\/j.ejphar.2025.178026_bib50","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.7150\/thno.19500","article-title":"Melatonin suppresses neuropathic pain via MT2-dependent and -independent pathways in dorsal root ganglia neurons of mice","volume":"7","author":"Lin","year":"2017","journal-title":"Theranostics"},{"issue":"3","key":"10.1016\/j.ejphar.2025.178026_bib51","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1111\/jpi.12307","article-title":"Melatonin relieves neuropathic allodynia through spinal MT2-enhanced PP2Ac and downstream HDAC4 shuttling-dependent epigenetic modification of hmgb1 transcription","volume":"60","author":"Lin","year":"2016","journal-title":"J. Pineal Res."},{"issue":"3","key":"10.1016\/j.ejphar.2025.178026_bib52","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1111\/jpi.12307","article-title":"Melatonin relieves neuropathic allodynia through spinal MT2-enhanced PP2Ac and downstream HDAC4 shuttling-dependent epigenetic modification of hmgb1 transcription","volume":"60","author":"Lin","year":"2016","journal-title":"J. Pineal Res."},{"issue":"20","key":"10.1016\/j.ejphar.2025.178026_bib53","doi-asserted-by":"crossref","first-page":"3973","DOI":"10.1007\/s00213-014-3530-5","article-title":"Piromelatine exerts antinociceptive effect via melatonin, opioid, and 5HT1A receptors and hypnotic effect via melatonin receptors in a mouse model of neuropathic pain","volume":"231","author":"Liu","year":"2014","journal-title":"Psychopharmacology (Berl)"},{"key":"10.1016\/j.ejphar.2025.178026_bib54","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2015.07.010","article-title":"Antinociceptive properties of selective MT2 melatonin receptor partial agonists","volume":"764","author":"Lopez-Canul","year":"2015","journal-title":"Eur. J. Pharmacol."},{"issue":"2","key":"10.1016\/j.ejphar.2025.178026_bib55","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1097\/01.j.pain.0000460311.71572.5f","article-title":"Selective melatonin MT2 receptor ligands relieve neuropathic pain through modulation of brainstem descending antinociceptive pathways","volume":"156","author":"Lopez-Canul","year":"2015","journal-title":"Pain"},{"key":"10.1016\/j.ejphar.2025.178026_bib56","doi-asserted-by":"crossref","DOI":"10.1177\/17448069231170072","article-title":"Melatonin attenuated chronic visceral pain by reducing Nav1.8 expression and nociceptive neuronal sensitization","volume":"19","author":"Lv","year":"2023","journal-title":"Mol. Pain"},{"key":"10.1016\/j.ejphar.2025.178026_bib57","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1111\/j.1600-079X.2006.00380.x","article-title":"Mechanisms involved in the antinociception caused by melatonin in mice","volume":"41","author":"Mantovani","year":"2006","journal-title":"J. Pineal Res."},{"issue":"1\u20132","key":"10.1016\/j.ejphar.2025.178026_bib58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/03602532.2023.2177671","article-title":"Effects of xenobiotics on CYP1 enzyme-mediated biotransformation and bioactivation of estradiol","volume":"55","author":"Mao","year":"2023","journal-title":"Drug Metab. Rev."},{"issue":"22","key":"10.1016\/j.ejphar.2025.178026_bib59","doi-asserted-by":"crossref","DOI":"10.3390\/ijms222212143","article-title":"Possible role of pineal and extra-pineal melatonin in surveillance, immunity, and first-line defense","volume":"22","author":"Markus","year":"2021","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.ejphar.2025.178026_bib60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-079X.2012.01014.x","article-title":"A review of the molecular aspects of melatonin's anti-inflammatory actions: recent insights and new perspectives","volume":"54","author":"Mauriz","year":"2013","journal-title":"J. Pineal Res."},{"issue":"4","key":"10.1016\/j.ejphar.2025.178026_bib61","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/1056-8719(94)90087-6","article-title":"A method to perform direct transcutaneous intrathecal injection in rats","volume":"32","author":"Mestre","year":"1994","journal-title":"J. Pharmacol. Toxicol. Methods"},{"issue":"24","key":"10.1016\/j.ejphar.2025.178026_bib62","doi-asserted-by":"crossref","first-page":"4230","DOI":"10.1021\/jm010254a","article-title":"Estrogen receptor-beta potency-selective ligands: structure-activity relationship studies of diarylpropionitriles and their acetylene and polar analogues","volume":"44","author":"Meyers","year":"2001","journal-title":"J. Med. Chem."},{"issue":"3","key":"10.1016\/j.ejphar.2025.178026_bib63","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.pain.2010.03.030","article-title":"Antinociceptive effects of melatonin in a rat model of post-inflammatory visceral hyperalgesia: a centrally mediated process","volume":"149","author":"Mickle","year":"2010","journal-title":"Pain"},{"issue":"12","key":"10.1016\/j.ejphar.2025.178026_bib64","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/nrn3360","article-title":"Sex differences in pain and pain inhibition: multiple explanations of a controversial phenomenon","volume":"13","author":"Mogil","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.ejphar.2025.178026_bib65","first-page":"141","article-title":"Sex and gender differences in pain and analgesia","volume":"186","author":"Mogil","year":"2010","journal-title":"Prog. Brain Res."},{"key":"10.1016\/j.ejphar.2025.178026_bib66","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/1744-8069-6-34","article-title":"Hypolocomotion, asymmetrically directed behaviors (licking, lifting, flinching, and shaking) and dynamic weight bearing (gait) changes are not measures of neuropathic pain in mice","volume":"6","author":"Mogil","year":"2010","journal-title":"Mol. Pain"},{"key":"10.1016\/j.ejphar.2025.178026_bib67","doi-asserted-by":"crossref","DOI":"10.1016\/j.neubiorev.2024.105749","article-title":"Sex differences in mechanisms of pain hypersensitivity","volume":"163","author":"Mogil","year":"2024","journal-title":"Neurosci. Biobehav. Rev."},{"issue":"1","key":"10.1016\/j.ejphar.2025.178026_bib68","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1038\/s41598-023-28418-1","article-title":"Exogenous melatonin alleviates neuropathic pain-induced affective disorders by suppressing NF-kappa B\/NLRP3 pathway and apoptosis","volume":"13","author":"Mokhtari","year":"2023","journal-title":"Sci. Rep."},{"issue":"4","key":"10.1016\/j.ejphar.2025.178026_bib69","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1002\/ddr.21528","article-title":"Cerebrolysin improves peripheral inflammatory pain: sex differences in two models of acute and chronic mechanical hypersensitivity","volume":"80","author":"Morales-Medina","year":"2019","journal-title":"Drug Dev. Res."},{"key":"10.1016\/j.ejphar.2025.178026_bib70","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.neuroscience.2014.02.040","article-title":"Activation of Gq-coupled membrane estrogen receptor rapidly attenuates \u03b12-adrenoreceptor-induced antinociception via an ERK I\/II-dependent, non-genomic mechanism in the female rat","volume":"267","author":"Nag","year":"2014","journal-title":"Neuroscience"},{"issue":"7","key":"10.1016\/j.ejphar.2025.178026_bib71","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1007\/s00429-017-1439-6","article-title":"Melatonin receptors: distribution in mammalian brain and their respective putative functions","volume":"222","author":"Ng","year":"2017","journal-title":"Brain Struct. Funct."},{"key":"10.1016\/j.ejphar.2025.178026_bib72","first-page":"35","article-title":"Intrathecal melatonin increases the mechanical nociceptive threshold in the rat","volume":"16","author":"Onal","year":"2004","journal-title":"Agriculture"},{"issue":"14","key":"10.1016\/j.ejphar.2025.178026_bib73","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202400320R","article-title":"Sex hormone deprivation abolishes sex-specific differences in murine colon inflammation and related lipid mediator production","volume":"38","author":"Pace","year":"2024","journal-title":"FASEB J."},{"key":"10.1016\/j.ejphar.2025.178026_bib74","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1159\/000109138","article-title":"Melatonin receptors in the spinal cord","volume":"6","author":"Pang","year":"1997","journal-title":"Biol. Signals"},{"key":"10.1016\/j.ejphar.2025.178026_bib75","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.physbeh.2014.04.016","article-title":"Potential drug interactions with melatonin","volume":"131","author":"Papagiannidou","year":"2014","journal-title":"Physiol. Behav."},{"issue":"2","key":"10.1016\/j.ejphar.2025.178026_bib76","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/0166-4328(84)90141-4","article-title":"Sex and strain related effects of melatonin and 5-methoxytryptophol on open field behaviour in paired mice","volume":"13","author":"Paterson","year":"1984","journal-title":"Behav. Brain Res."},{"issue":"4","key":"10.1016\/j.ejphar.2025.178026_bib77","doi-asserted-by":"crossref","DOI":"10.1111\/jpi.12825","article-title":"Supraspinal melatonin MT2 receptor agonism alleviates pain via a neural circuit that recruits mu opioid receptors","volume":"73","author":"Posa","year":"2022","journal-title":"J. Pineal Res."},{"issue":"3","key":"10.1016\/j.ejphar.2025.178026_bib78","doi-asserted-by":"crossref","DOI":"10.1111\/jpi.12671","article-title":"Nociceptive responses in melatonin MT2 receptor knockout mice compared to MT1 and double MT1\/MT2 receptor knockout mice","volume":"69","author":"Posa","year":"2020","journal-title":"J. Pineal Res."},{"key":"10.1016\/j.ejphar.2025.178026_bib79","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0014-2999(00)00196-5","article-title":"Melatonin reversal of lipopolysacharides-induced thermal and behavioral hyperalgesia in mice","volume":"395","author":"Raghavendra","year":"2000","journal-title":"Eur. J. Pharmacol."},{"issue":"2","key":"10.1016\/j.ejphar.2025.178026_bib80","doi-asserted-by":"crossref","DOI":"10.1016\/S0026-895X(25)09932-8","article-title":"Pharmacological characterization of the cloned kappa-, delta-, and mu-opioid receptors","volume":"45","author":"Raynor","year":"1994","journal-title":"Mol. Pharmacol."},{"issue":"4","key":"10.1016\/j.ejphar.2025.178026_bib81","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1080\/17446651.2023.2237103","article-title":"Melatonin modulates tumor metabolism and mitigates metastasis","volume":"18","author":"Reiter","year":"2023","journal-title":"Expet Rev. Endocrinol. Metabol."},{"issue":"3","key":"10.1016\/j.ejphar.2025.178026_bib82","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/0165-6147(96)10005-5","article-title":"Melatonin receptors step into the light: cloning and classification of subtypes","volume":"17","author":"Reppert","year":"1996","journal-title":"Trends Pharmacol. Sci."},{"issue":"3","key":"10.1016\/j.ejphar.2025.178026_bib83","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1021\/acs.jnatprod.0c00793","article-title":"Pharmacological analysis of the anti-inflammatory and antiallodynic effects of zinagrandinolide E from Zinnia grandiflora in mice","volume":"84","author":"Reyes-P\u00e9rez","year":"2021","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.ejphar.2025.178026_bib84","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2022.174855","article-title":"Sex-dependent antiallodynic effect of \u03b12 adrenergic receptor agonist tizanidine in rats with experimental neuropathic pain","volume":"920","author":"Rodr\u00edguez-Palma","year":"2022","journal-title":"Eur. J. Pharmacol."},{"issue":"5","key":"10.1016\/j.ejphar.2025.178026_bib85","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1097\/j.pain.0000000000002763","article-title":"Activation of \u03b16-containing GABAA receptors induces antinociception under physiological and pathological conditions","volume":"164","author":"Rodr\u00edguez-Palma","year":"2023","journal-title":"Pain"},{"key":"10.1016\/j.ejphar.2025.178026_bib86","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejphar.2024.176616","article-title":"Estradiol modulates the role of the spinal \u03b16-subunit containing GABAA receptors in female rats with neuropathic pain","volume":"974","author":"Rodr\u00edguez-Palma","year":"2024","journal-title":"Eur. J. Pharmacol."},{"issue":"1\u20132","key":"10.1016\/j.ejphar.2025.178026_bib87","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1002\/jnr.23831","article-title":"Sex differences in neuroimmunity and pain","volume":"95","author":"Rosen","year":"2017","journal-title":"J. Neurosci. Res."},{"issue":"4","key":"10.1016\/j.ejphar.2025.178026_bib88","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1002\/ejp.1907","article-title":"The glial cell's role in antinociceptive differential effects of oxytocin upon female and male rats","volume":"26","author":"Salinas-Abarca","year":"2022","journal-title":"Eur. J. Pain"},{"issue":"5","key":"10.1016\/j.ejphar.2025.178026_bib89","doi-asserted-by":"crossref","first-page":"317","DOI":"10.2170\/physiolsci.RP006208","article-title":"Sexually dimorphic modulation of GABAA receptor currents by melatonin in rat gonadotropin-releasing hormone neurons","volume":"58","author":"Sato","year":"2008","journal-title":"J. Physiol. Sci."},{"issue":"8","key":"10.1016\/j.ejphar.2025.178026_bib90","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1021\/jm020536q","article-title":"De novo design, synthesis, and evaluation of novel nonsteroidal phenanthrene ligands for the estrogen receptor","volume":"6","author":"Schmidt","year":"2003","journal-title":"J. Med. Chem."},{"issue":"2","key":"10.1016\/j.ejphar.2025.178026_bib91","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.mce.2012.01.004","article-title":"Melatonin membrane receptors in peripheral tissues: distribution and functions","volume":"351","author":"Slominski","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"issue":"26","key":"10.1016\/j.ejphar.2025.178026_bib92","doi-asserted-by":"crossref","first-page":"4934","DOI":"10.1021\/jm000170m","article-title":"Pyrazole ligands: structure-affinity\/activity relationships and estrogen receptor-alpha-selective agonists","volume":"43","author":"Stauffer","year":"2000","journal-title":"J. Med. Chem."},{"issue":"3","key":"10.1016\/j.ejphar.2025.178026_bib93","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1210\/endo.143.3.8704","article-title":"Antagonists selective for estrogen receptor \u03b1","volume":"143","author":"Sun","year":"2002","journal-title":"Endocrinology"},{"issue":"4","key":"10.1016\/j.ejphar.2025.178026_bib94","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.maturitas.2014.01.015","article-title":"The effect of hormone therapy on serum melatonin concentrations in premenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled study","volume":"77","author":"Toffol","year":"2014","journal-title":"Maturitas"},{"key":"10.1016\/j.ejphar.2025.178026_bib95","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.pain.2004.01.027","article-title":"Effects of intrathecal injections of melatonin analogs on capsaicin-induced secondary mechanical allodynia and hyperalgesia in rats","volume":"109","author":"Tu","year":"2004","journal-title":"Pain"},{"issue":"18","key":"10.1016\/j.ejphar.2025.178026_bib96","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.3390\/cells11182809","article-title":"Melatonin attenuates spinal cord injury in mice by activating the Nrf2\/ARE signaling pathway to inhibit the NLRP3 inflammasome","volume":"11","author":"Wang","year":"2022","journal-title":"Cells"},{"issue":"6","key":"10.1016\/j.ejphar.2025.178026_bib97","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1007\/s10753-017-0645-y","article-title":"Melatonin attenuates pain hypersensitivity and decreases astrocyte-mediated spinal neuroinflammation in a rat model of oxaliplatin-induced pain","volume":"40","author":"Wang","year":"2017","journal-title":"Inflammation"},{"issue":"1","key":"10.1016\/j.ejphar.2025.178026_bib98","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3892\/etm.2023.12325","article-title":"Melatonin exerts neuroprotective effects in mice with spinal cord injury by activating the Nrf2\/Keap1 signaling pathway via the MT2 receptor","volume":"27","author":"Yan","year":"2023","journal-title":"Exp. Ther. Med."},{"key":"10.1016\/j.ejphar.2025.178026_bib99","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuropharm.2022.109254","article-title":"Melatonin attenuates bone cancer pain via the SIRT1\/HMGB1 pathway","volume":"220","author":"Yang","year":"2022","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.ejphar.2025.178026_bib100","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.yjmcc.2018.10.018","article-title":"Melatonin attenuates chronic pain related myocardial ischemic susceptibility through inhibiting RIP3-MLKL\/CaMKII dependent necroptosis","volume":"125","author":"Yang","year":"2018","journal-title":"J. Mol. Cell. Cardiol."},{"issue":"1","key":"10.1016\/j.ejphar.2025.178026_bib101","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/s41398-023-02614-z","article-title":"Melatonin alleviates depression-like behaviors and cognitive dysfunction in mice by regulating the circadian rhythm of AQP4 polarization","volume":"13","author":"Yao","year":"2023","journal-title":"Transl. Psychiatry"},{"key":"10.1016\/j.ejphar.2025.178026_bib102","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/S0014-2999(00)00421-0","article-title":"The analgesic effects of peripheral and central administration of melatonin in rats","volume":"403","author":"Yu","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.ejphar.2025.178026_bib103","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.saa.2017.09.042","article-title":"New insights on the spectrophotometric determination of melatonin pKa values and melatonin-\u03b2CD inclusion complex formation constant","volume":"190","author":"Zafra-Rold\u00e1n","year":"2018","journal-title":"Spectrochim. Acta Mol. Biomol. Spectrosc."},{"key":"10.1016\/j.ejphar.2025.178026_bib104","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.neuroscience.2023.10.005","article-title":"Melatonin improves mitochondrial dysfunction and attenuates neuropathic pain by regulating SIRT1 in dorsal root ganglions","volume":"534","author":"Zeng","year":"2023","journal-title":"Neuroscience"},{"issue":"1","key":"10.1016\/j.ejphar.2025.178026_bib105","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13293-019-0271-5","article-title":"Estrogen modulation of pain perception with a novel 17beta-estradiol pretreatment regime in ovariectomized rats","volume":"11","author":"Zhang","year":"2020","journal-title":"Biol. Sex Differ."},{"issue":"4","key":"10.1016\/j.ejphar.2025.178026_bib106","doi-asserted-by":"crossref","DOI":"10.1111\/jpi.12476","article-title":"Melatonin-mediated inhibition of Cav3.2 T-type Ca2+ channels induces sensory neuronal hypoexcitability through the novel protein kinase C-eta isoform","volume":"64","author":"Zhang","year":"2018","journal-title":"J. Pineal Res."},{"key":"10.1016\/j.ejphar.2025.178026_bib107","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0304-3959(83)90201-4","article-title":"Ethical guidelines for investigations of experimental pain in conscious animals","volume":"16","author":"Zimmermann","year":"1983","journal-title":"Pain"},{"issue":"6","key":"10.1016\/j.ejphar.2025.178026_bib108","first-page":"641","article-title":"Exogenous melatonin abolishes mechanical allodynia but not thermal hyperalgesia in neuropathic pain. The role of the opioid system and benzodiazepine-GABAergic mechanism","volume":"63","author":"Zurowski","year":"2012","journal-title":"J. Physiol. Pharmacol."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299925007800?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299925007800?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T07:33:16Z","timestamp":1772782396000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299925007800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":106,"alternative-id":["S0014299925007800"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.178026","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Activation of spinal melatonin MT2 receptors reduces neuropathic pain in mice in a sex-dependent manner","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2025.178026","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"178026"}}