{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:13:48Z","timestamp":1790813628696,"version":"4.1.0"},"reference-count":81,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T00:00:00Z","timestamp":1604188800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T00:00:00Z","timestamp":1596240000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001870","name":"Fundacja na rzecz Nauki Polskiej","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001870","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004569","name":"Ministerstwo Nauki i Szkolnictwa Wy\u017cszego","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004569","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005243","name":"United Nations Educational, Scientific and Cultural Organization","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["MAESTRO 2012\/06\/A\/NZ4\/00028"],"award-info":[{"award-number":["MAESTRO 2012\/06\/A\/NZ4\/00028"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2018\/29\/B\/NZ7\/00082"],"award-info":[{"award-number":["2018\/29\/B\/NZ7\/00082"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neuropharmacology"],"published-print":{"date-parts":[[2020,11]]},"DOI":"10.1016\/j.neuropharm.2020.108232","type":"journal-article","created":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T11:58:31Z","timestamp":1596283111000},"page":"108232","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":20,"special_numbering":"C","title":["Novel hybrid compounds, opioid agonist+melanocortin 4 receptor antagonist, as efficient analgesics in mouse chronic constriction injury model of neuropathic pain"],"prefix":"10.1016","volume":"178","author":[{"given":"Joanna","family":"Starnowska-Sok\u00f3\u0142","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Piotrowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Bogacka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wioletta","family":"Makuch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Mika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Witkowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda","family":"Godlewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jowita","family":"Osiejuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"G\u0105tarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Misicka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Przew\u0142ocka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.neuropharm.2020.108232_bib1","doi-asserted-by":"crossref","first-page":"668","DOI":"10.2174\/092986608785133672","article-title":"Multiple ligands in opioid research","volume":"15","author":"Ballet","year":"2008","journal-title":"Protein Pept. Lett."},{"key":"10.1016\/j.neuropharm.2020.108232_bib2","series-title":"Mol. Pain","article-title":"Clinical opioids differentially induce co-internalization of \u03bc- and \u03b4-opioid receptors","author":"Bao","year":"2018"},{"key":"10.1016\/j.neuropharm.2020.108232_bib3","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ejphar.2003.09.017","article-title":"Melanocortin receptor agonists and antagonists modulate nociceptive sensitivity in the mouse formalin test","volume":"482","author":"Bellasio","year":"2003","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.neuropharm.2020.108232_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.molbrainres.2003.08.001","article-title":"Gene expression profiling of melanocortin system in neuropathic rats supports a role in nociception","author":"Beltramo","year":"2003","journal-title":"Mol. Brain Res."},{"key":"10.1016\/j.neuropharm.2020.108232_bib5","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0304-3959(88)90209-6","article-title":"A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man","volume":"33","author":"Bennett","year":"1988","journal-title":"Pain"},{"key":"10.1016\/j.neuropharm.2020.108232_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbr.2004.06.008","article-title":"Endogenous and exogenous melanocortin antagonists induce anti-allodynic effects in a model of rat neuropathic pain","author":"Bertorelli","year":"2005","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.neuropharm.2020.108232_bib7","doi-asserted-by":"crossref","DOI":"10.1021\/acsmedchemlett.5b00359","article-title":"Dual alleviation of acute and neuropathic pain by fused opioid agonist-neurokinin 1 antagonist peptidomimetics","author":"Betti","year":"2015","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.neuropharm.2020.108232_bib8","doi-asserted-by":"crossref","first-page":"339","DOI":"10.4155\/fmc.15.186","article-title":"Opioid adjuvant strategy: improving opioid effectiveness","volume":"8","author":"Bihel","year":"2016","journal-title":"Future Med. Chem."},{"key":"10.1016\/j.neuropharm.2020.108232_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.tips.2006.11.003","article-title":"Trafficking of \u03b4-opioid receptors and other G-protein-coupled receptors: implications for pain and analgesia","author":"Cahill","year":"2007","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.neuropharm.2020.108232_bib10","doi-asserted-by":"crossref","DOI":"10.2174\/1389203717666160226145330","article-title":"The melanocortin receptor system: a target for multiple degenerative diseases","author":"Cai","year":"2016","journal-title":"Curr. Protein Pept. Sci."},{"key":"10.1016\/j.neuropharm.2020.108232_bib11","article-title":"\u03bc-Opioid receptor inhibition of substance P release from primary afferents disappears in neuropathic pain but not inflammatory pain","author":"Chen","year":"2014","journal-title":"Neuroscience"},{"key":"10.1016\/j.neuropharm.2020.108232_bib12","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1179\/1743132812Y.0000000085","article-title":"Effect of periaqueductal gray melanocortin 4 receptor in pain facilitation and glial activation in rat model of chronic constriction injury","volume":"34","author":"Chu","year":"2012","journal-title":"Neurol. Res."},{"key":"10.1016\/j.neuropharm.2020.108232_bib13","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1017\/S0317167100013962","article-title":"Melanocortin 4 receptor mediates neuropathic pain through p38MAPK in spinal cord","volume":"39","author":"Chu","year":"2012","journal-title":"Can. J. Neurol. Sci."},{"key":"10.1016\/j.neuropharm.2020.108232_bib14","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3109\/00207454.2011.630542","article-title":"Melanocortin 4 receptor induces hyperalgesia and allodynia after chronic constriction injury by activation of p38 MAPK in DRG","volume":"122","author":"Chu","year":"2012","journal-title":"Int. J. Neurosci."},{"key":"10.1016\/j.neuropharm.2020.108232_bib15","doi-asserted-by":"crossref","DOI":"10.1038\/nrdp.2017.2","article-title":"Neuropathic pain","author":"Colloca","year":"2017","journal-title":"Nat. Rev. Dis. Prim"},{"key":"10.1016\/j.neuropharm.2020.108232_bib16","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.2174\/1568026616666160927160620","article-title":"Hybrid compounds as direct multitarget ligands: a review","volume":"17","author":"de Oliveira Pedrosa","year":"2017","journal-title":"Curr. Top. Med. Chem."},{"key":"10.1016\/j.neuropharm.2020.108232_bib17","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1749-6632.2010.05928.x","article-title":"Evolution of POMC: origin, phylogeny, posttranslational processing, and the melanocortins","volume":"1220","author":"Dores","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.neuropharm.2020.108232_bib18","doi-asserted-by":"crossref","DOI":"10.1016\/j.pain.2007.08.033","article-title":"Pharmacologic management of neuropathic pain: evidence-based recommendations","author":"Dworkin","year":"2007","journal-title":"Pain"},{"key":"10.1016\/j.neuropharm.2020.108232_bib19","doi-asserted-by":"crossref","DOI":"10.1210\/edrv-1-1-1","article-title":"Structure and biosynthesis of pro-adrenocorticotropin\/endorphin and related peptides","author":"Eipper","year":"1980","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.neuropharm.2020.108232_bib20","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s00213-005-2166-x","article-title":"HS014, a selective melanocortin-4 (MC4) receptor antagonist, modulates the behavioral effects of morphine in mice","volume":"180","author":"Ercil","year":"2005","journal-title":"Psychopharmacology (Berlin)"},{"key":"10.1016\/j.neuropharm.2020.108232_bib21","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/S0169-409X(03)00101-7","article-title":"Spinal delivery of analgesics in experimental models of pain and analgesia","volume":"55","author":"Fairbanks","year":"2003","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.neuropharm.2020.108232_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2014.09.055","article-title":"Synthesis and evaluation of bivalent ligands for binding to the human melanocortin-4 receptor","author":"Fernandes","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.neuropharm.2020.108232_bib23","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(14)70251-0","article-title":"Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis","volume":"14","author":"Finnerup","year":"2015","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.neuropharm.2020.108232_bib24","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s40122-017-0091-4","article-title":"Pharmacotherapy for neuropathic pain: a review","volume":"6","author":"Fornasari","year":"2017","journal-title":"Pain Ther"},{"key":"10.1016\/j.neuropharm.2020.108232_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/S1046-2023(02)00094-4","article-title":"Oligomerization of opioid receptors","author":"Gomes","year":"2002","journal-title":"Methods"},{"key":"10.1016\/j.neuropharm.2020.108232_bib26","doi-asserted-by":"crossref","DOI":"10.1124\/mol.106.028258","article-title":"An opioid agonist that does not induce \u03bc-opioid receptor - arrestin interactions or receptor internalization","author":"Groer","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.neuropharm.2020.108232_bib27","doi-asserted-by":"crossref","first-page":"3777","DOI":"10.1021\/acs.jmedchem.5b01976","article-title":"Bifunctional peptide-based opioid agonist\u2013nociceptin antagonist ligands for dual treatment of acute and neuropathic pain HHS public access","volume":"59","author":"Guillemyn","year":"2016","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.neuropharm.2020.108232_bib28","doi-asserted-by":"crossref","DOI":"10.1523\/JNEUROSCI.5045-04.2005","article-title":"Morphine promotes rapid, arrestin-dependent endocytosis of \u03bc-opioid receptors in striatal neurons","author":"Haberstock-Debic","year":"2005","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuropharm.2020.108232_bib29","doi-asserted-by":"crossref","DOI":"10.1523\/JNEUROSCI.23-10-04324.2003","article-title":"Morphine acutely regulates opioid receptor trafficking selectively in dendrites of nucleus accumbens neurons","author":"Haberstock-Debic","year":"2003","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuropharm.2020.108232_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.brainres.2011.04.024","article-title":"Novel peptide ligands with dual acting pharmacophores designed for the pathophysiology of neuropathic pain","author":"Hanlon","year":"2011","journal-title":"Brain Res."},{"key":"10.1016\/j.neuropharm.2020.108232_bib31","doi-asserted-by":"crossref","DOI":"10.1096\/fj.09-133223","article-title":"Biomarkers of morphine tolerance and dependence are prevented by morphine\u2010induced endocytosis of a mutant \u03bc\u2010opioid receptor","author":"He","year":"2009","journal-title":"Faseb. J."},{"key":"10.1016\/j.neuropharm.2020.108232_bib32","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/S0024-3205(03)00390-4","article-title":"Design of novel peptide ligands which have opioid agonist activity and CCK antagonist activity for the treatment of pain","volume":"73","author":"Hruby","year":"2003","journal-title":"Life Sci."},{"key":"10.1016\/j.neuropharm.2020.108232_bib33","doi-asserted-by":"crossref","first-page":"3454","DOI":"10.1021\/jm00018a005","article-title":"Cyclic lactam alpha-melanotropin analogues of Ac-Nle4-cyclo[Asp5, D-Phe7,Lys10] alpha-melanocyte-stimulating hormone-(4-10)-NH2 with bulky aromatic amino acids at position 7 show high antagonist potency and selectivity at specific melanocortin receptors","volume":"38","author":"Hruby","year":"1995","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.neuropharm.2020.108232_bib34","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/0014-2999(80)90515-4","article-title":"Intrathecal morphine in mice: a new technique","volume":"67","author":"Hylden","year":"1980","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.neuropharm.2020.108232_bib35","doi-asserted-by":"crossref","DOI":"10.1111\/j.1533-2500.2006.00055.x","article-title":"Pharmacotherapy for neuropathic pain","author":"Jackson","year":"2006","journal-title":"Pain Pract."},{"key":"10.1016\/j.neuropharm.2020.108232_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.neulet.2013.03.026","article-title":"Role of spinal opioid receptor on the antiallodynic effect of intrathecal nociceptin in neuropathic rat","author":"Ju","year":"2013","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.neuropharm.2020.108232_bib37","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.brainres.2007.08.054","article-title":"Central administration of selective melanocortin 4 receptor antagonist HS014 prevents morphine tolerance and withdrawal hyperalgesia","volume":"1181","author":"Kalange","year":"2007","journal-title":"Brain Res."},{"key":"10.1016\/j.neuropharm.2020.108232_bib38","doi-asserted-by":"crossref","DOI":"10.1124\/mol.53.3.377","article-title":"\u03bc-opioid receptor internalization: opiate drugs have differential effects on a conserved endocytic mechanism in vitro and in the mammalian brain","author":"Keith","year":"1998","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.neuropharm.2020.108232_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.cub.2007.12.057","article-title":"Morphine-induced receptor endocytosis in a novel knockin mouse reduces tolerance and dependence","author":"Kim","year":"2008","journal-title":"Curr. Biol."},{"key":"10.1016\/j.neuropharm.2020.108232_bib40","article-title":"Effect of exercise on \u03bc-opioid receptor expression in the rostral ventromedial medulla in neuropathic pain rat model","author":"Kim","year":"2015","journal-title":"Ann. Rehabil. Med"},{"key":"10.1016\/j.neuropharm.2020.108232_bib41","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/978-0-387-73657-0_90","article-title":"Novel analogues of bifunctional ligands for opioid and melanocortin 4 receptor","volume":"611","author":"Kulkarni","year":"2009","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.neuropharm.2020.108232_bib42","series-title":"Journal of Pharmacology and Experimental Therapeutics","article-title":"Regulation of opioid receptor activities","author":"Law","year":"1999"},{"key":"10.1016\/j.neuropharm.2020.108232_bib43","article-title":"Dynamic temporal and spatial regulation of mu opioid receptor expression in primary afferent neurons following spinal nerve injury","author":"Lee","year":"2011","journal-title":"Eur. J. Pain"},{"key":"10.1016\/j.neuropharm.2020.108232_bib44","article-title":"Design and synthesis of trivalent ligands targeting opioid, cholecystokinin, and melanocortin receptors for the treatment of pain","author":"Lee","year":"2010","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.neuropharm.2020.108232_bib45","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1016\/j.bbadis.2017.05.021","article-title":"Melanocortin-4 receptor regulation of painLi Z-X, Liu B-W, He Z-G, Xiang H-B (2017) Melanocortin-4 receptor regulation of pain","volume":"1863","author":"Li","year":"2017","journal-title":"Biochim. Biophys. Acta (BBA) - Mol. Basis Dis."},{"key":"10.1016\/j.neuropharm.2020.108232_bib46","doi-asserted-by":"crossref","DOI":"10.1016\/j.conb.2007.10.004","article-title":"The role of mu opioid receptor desensitization and endocytosis in morphine tolerance and dependence","author":"Martini","year":"2007","journal-title":"Curr. Opin. Neurobiol."},{"key":"10.1016\/j.neuropharm.2020.108232_bib47","doi-asserted-by":"crossref","DOI":"10.1016\/0024-3205(78)90396-X","article-title":"Potent analgesic activity of the enkephalin-like tetrapeptide H-Tyr-D-Ala-Gly-Phe-NH2","author":"McGregor","year":"1978","journal-title":"Life Sci."},{"key":"10.1016\/j.neuropharm.2020.108232_bib48","doi-asserted-by":"crossref","DOI":"10.1021\/jm058225d","article-title":"Designed multiple ligands. An emerging drug discovery paradigm","author":"Morphy","year":"2005","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.neuropharm.2020.108232_bib49","doi-asserted-by":"crossref","DOI":"10.1038\/278423a0","article-title":"Nucleotide sequence of cloned cDNA for bovine corticotropin-\u03b2- lipotropin precursor","author":"Nakanishi","year":"1979","journal-title":"Nature"},{"key":"10.1016\/j.neuropharm.2020.108232_bib50","doi-asserted-by":"crossref","DOI":"10.1111\/bph.12761","article-title":"Prolonged morphine treatment alters \u03b4 opioid receptor post-internalization trafficking","author":"Ong","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.neuropharm.2020.108232_bib51","doi-asserted-by":"crossref","DOI":"10.1097\/SPC.0000000000000055","article-title":"Descending pain modulation and chronification of pain","author":"Ossipov","year":"2014","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"10.1016\/j.neuropharm.2020.108232_bib52","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1111\/j.1533-2500.2010.00378.x","article-title":"Current knowledge of buprenorphine and its unique pharmacological profile","volume":"10","author":"Pergolizzi","year":"2010","journal-title":"Pain Pract."},{"key":"10.1016\/j.neuropharm.2020.108232_bib53","unstructured":"Piotrowska, A., Starnowska, J., Makuch, W., Mika, J., Witkowska, E., Tymecka, D., Wilenska, B., Ignaczak, A., Misicka, A., Przew\u0142ocka, B., n.d. Novel bifunctional hybrid compounds as potent analgesics in rat model of neuropathic pain designed to enhance the opioid, and antagonize the non-opioid pronociceptive effects. Pain."},{"key":"10.1016\/j.neuropharm.2020.108232_bib54","doi-asserted-by":"crossref","DOI":"10.1523\/JNEUROSCI.3748-10.2010","article-title":"Ligand-directed trafficking of the \u03b4-opioid receptor in vivo: two paths toward analgesic tolerance","author":"Pradhan","year":"2010","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuropharm.2020.108232_bib55","doi-asserted-by":"crossref","DOI":"10.2174\/1381612054865055","article-title":"Opioids in neuropathic pain","author":"Przewlocki","year":"2005","journal-title":"Curr. Pharmaceut. Des."},{"key":"10.1016\/j.neuropharm.2020.108232_bib56","article-title":"Cebranopadol: novel dual opioid\/NOP receptor agonist analgesic","author":"Raffa","year":"2016","journal-title":"J. Clin. Pharm. Therapeut."},{"key":"10.1016\/j.neuropharm.2020.108232_bib57","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.lfs.2009.02.025","article-title":"Bi- or multifunctional opioid peptide drugs","volume":"86","author":"Schiller","year":"2010","journal-title":"Life Sci."},{"key":"10.1016\/j.neuropharm.2020.108232_bib58","doi-asserted-by":"crossref","DOI":"10.2147\/JPR.S130654","article-title":"DNMT3a methylation in neuropathic pain","author":"Shao","year":"2017","journal-title":"J. Pain Res."},{"key":"10.1016\/j.neuropharm.2020.108232_bib59","doi-asserted-by":"crossref","DOI":"10.1016\/S0169-328X(98)00133-8","article-title":"The effects of antisense to G(i\u03b12) on opioid agonist potency and G(i\u03b12) protein and mRNA abundance in the mouse","author":"Shen","year":"1998","journal-title":"Mol. Brain Res."},{"key":"10.1016\/j.neuropharm.2020.108232_bib60","doi-asserted-by":"crossref","DOI":"10.1210\/en.2002-220931","article-title":"Regulation of melanocortin-4 receptor signaling: agonist-mediated desensitization and internalization","author":"Shinyama","year":"2003","journal-title":"Endocrinology"},{"key":"10.1016\/j.neuropharm.2020.108232_bib61","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.neulet.2003.12.096","article-title":"Melanocortin 4 receptor is expressed in the dorsal root ganglions and down-regulated in neuropathic rats","volume":"358","author":"Starowicz","year":"2004","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.neuropharm.2020.108232_bib62","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/S1734-1140(09)70171-9","article-title":"Peripheral antinociceptive effects of MC4 receptor antagonists in a rat model of neuropathic pain - a biochemical and behavioral study","volume":"61","author":"Starowicz","year":"2009","journal-title":"Pharmacol. reports"},{"key":"10.1016\/j.neuropharm.2020.108232_bib63","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.pain.2005.07.003","article-title":"Inhibition of morphine tolerance by spinal melanocortin receptor blockade","volume":"117","author":"Starowicz","year":"2005","journal-title":"Pain"},{"key":"10.1016\/j.neuropharm.2020.108232_bib64","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1097\/00001756-200212200-00015","article-title":"Modulation of melanocortin-induced changes in spinal nociception by mu-opioid receptor agonist and antagonist in neuropathic rats","volume":"13","author":"Starowicz","year":"2002","journal-title":"Neuroreport"},{"key":"10.1016\/j.neuropharm.2020.108232_bib65","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0006-8993(03)03444-9","article-title":"The effect of morphine on MC4 and CRF receptor mRNAs in the rat amygdala and attenuation of tolerance after their blockade","volume":"990","author":"Starowicz","year":"2003","journal-title":"Brain Res."},{"key":"10.1016\/j.neuropharm.2020.108232_bib66","doi-asserted-by":"crossref","DOI":"10.1210\/er.2009-0037","article-title":"The melanocortin-4 receptor: physiology, pharmacology, and pathophysiology","author":"Tao","year":"2010","journal-title":"Endocr. Rev."},{"key":"10.1016\/j.neuropharm.2020.108232_bib67","doi-asserted-by":"crossref","first-page":"4506","DOI":"10.2174\/0929867323666161024151734","article-title":"Multitarget opioid\/non-opioid ligands: a potential approach in pain management","volume":"23","author":"Turnaturi","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.neuropharm.2020.108232_bib68","doi-asserted-by":"crossref","DOI":"10.1016\/j.mcna.2006.10.006","article-title":"Pathophysiology of pain","author":"Vanderah","year":"2007","journal-title":"Med. Clin. North Am."},{"key":"10.1016\/j.neuropharm.2020.108232_bib69","doi-asserted-by":"crossref","DOI":"10.1016\/S0304-3959(96)03225-3","article-title":"Single intrathecal injections of dynorphin A or des-Tyr-dynorphins produce long-lasting allodynia in rats: blockade by MK-801 but not naloxone","author":"Vanderah","year":"1996","journal-title":"Pain"},{"key":"10.1016\/j.neuropharm.2020.108232_bib70","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.2174\/092986707781058805","article-title":"Molecular hybridization: a useful tool in the design of new drug prototypes","volume":"14","author":"Viegas-Junior","year":"2007","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.neuropharm.2020.108232_bib71","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1097\/00000539-200112000-00052","article-title":"Chronic blockade of melanocortin receptors alleviates allodynia in rats with neuropathic pain","volume":"93","author":"Vrinten","year":"2001","journal-title":"Anesth. Analg."},{"key":"10.1016\/j.neuropharm.2020.108232_bib72","doi-asserted-by":"crossref","first-page":"8131","DOI":"10.1523\/JNEUROSCI.20-21-08131.2000","article-title":"Antagonism of the melanocortin system reduces cold and mechanical allodynia in mononeuropathic rats","volume":"20","author":"Vrinten","year":"2000","journal-title":"J. Neurosci."},{"key":"10.1016\/j.neuropharm.2020.108232_bib73","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1097\/00000542-200308000-00028","article-title":"Interaction between the spinal melanocortin and opioid systems in a rat model of neuropathic pain","volume":"99","author":"Vrinten","year":"2003","journal-title":"Anesthesiology"},{"key":"10.1016\/j.neuropharm.2020.108232_bib74","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuroscience.2013.08.069","article-title":"Activation of Mas oncogene-related gene (Mrg) C receptors enhances morphine-induced analgesia through modulation of coupling of \u03bc-opioid receptor to Gi-protein in rat spinal dorsal horn","author":"Wang","year":"2013","journal-title":"Neuroscience"},{"key":"10.1016\/j.neuropharm.2020.108232_bib75","doi-asserted-by":"crossref","DOI":"10.1016\/S0896-6273(01)80032-5","article-title":"Functional dissociation of \u03bc opioid receptor signaling and endocytosis: implications for the biology of opiate tolerance and addiction","author":"Whistler","year":"1999","journal-title":"Neuron"},{"key":"10.1016\/j.neuropharm.2020.108232_bib76","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1034\/j.1600-0773.2002.910619.x","article-title":"The role of spinal cholecystokinin in chronic pain states","volume":"91","author":"Wiesenfeld-Hallin","year":"2002","journal-title":"Pharmacol. Toxicol."},{"key":"10.1016\/j.neuropharm.2020.108232_bib77","doi-asserted-by":"crossref","first-page":"273","DOI":"10.17952\/35EPS.2018.273","article-title":"Hybrid peptidomimetics for the use in neuropathic pain","author":"Witkowska","year":"2018","journal-title":"Eur. Pept. Soc. PSP"},{"key":"10.1016\/j.neuropharm.2020.108232_bib78","doi-asserted-by":"crossref","DOI":"10.1016\/S0022-3565(24)35398-4","article-title":"Ligand-induced changes in surface \u03bc-opioid receptor number: relationship to G protein activation?","author":"Zaki","year":"2000","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.neuropharm.2020.108232_bib79","doi-asserted-by":"crossref","DOI":"10.1016\/0304-3959(83)90201-4","article-title":"Ethical guidelines for investigations of experimental pain in conscious animals","author":"Zimmermann","year":"1983","journal-title":"Pain"},{"key":"10.1016\/j.neuropharm.2020.108232_bib80","doi-asserted-by":"crossref","DOI":"10.1213\/01.ANE.0000160588.32007.AD","article-title":"The role of opioid receptor internalization and \u03b2-arrestins in the development of opioid tolerance","author":"Zuo","year":"2005","journal-title":"Anesth. Analg."},{"key":"10.1016\/j.neuropharm.2020.108232_bib81","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.pbb.2006.08.001","article-title":"The differential influences of melanocortins on nociception in the formalin and tail flick tests","volume":"85","author":"Zvejniece","year":"2006","journal-title":"Pharmacol. Biochem. Behav."}],"container-title":["Neuropharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0028390820303002?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0028390820303002?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:43:22Z","timestamp":1778643802000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0028390820303002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11]]},"references-count":81,"alternative-id":["S0028390820303002"],"URL":"https:\/\/doi.org\/10.1016\/j.neuropharm.2020.108232","relation":{},"ISSN":["0028-3908"],"issn-type":[{"value":"0028-3908","type":"print"}],"subject":[],"published":{"date-parts":[[2020,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Novel hybrid compounds, opioid agonist+melanocortin 4 receptor antagonist, as efficient analgesics in mouse chronic constriction injury model of neuropathic pain","name":"articletitle","label":"Article Title"},{"value":"Neuropharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.neuropharm.2020.108232","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"108232"}}