{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:57:08Z","timestamp":1791619028718,"version":"4.3.4"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pain Res."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Intermediate efficacy mu opioid receptor (MOR) agonists have potential to retain analgesic effectiveness while improving safety, but the optimal MOR efficacy for effective and safe opioid analgesia is unknown. Preclinical assays of pain-depressed behavior can assess effects of opioids and other candidate analgesics on pain-related behavioral depression, which is a common manifestation of clinically relevant pain and target of pain treatment. Accordingly, the present study goal was to validate a novel assay of pain-depressed locomotor behavior in mice and evaluate the role of MOR efficacy as a determinant of opioid analgesic effects and related safety measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male and female ICR mice were tested in a locomotor chamber consisting of 2 compartments connected by a doorway that contained a 1-inch-tall barrier. Dependent measures during 15-min behavioral sessions included crosses between compartments (which required vertical activity to surmount the barrier) and total movement counts (which required horizontal activity to break photobeams in each compartment).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Discussion<\/jats:title>\n                    <jats:p>Intraperitoneal injection of lactic acid (IP acid) produced a concentration- and time-dependent depression of both endpoints. Optimal blockade of IP acid-induced behavioral depression with minimal motor impairment was achieved with intermediate-efficacy MOR treatments that also produced less gastrointestinal-transit inhibition and respiratory depression than the high-efficacy MOR agonist fentanyl. Sex differences in treatment effects were rare. Overall, these findings validate a novel procedure for evaluating opioids and other candidate analgesic effects on pain-related behavioral depression in mice and support continued research with intermediate-efficacy MOR agonists as a strategy to retain opioid analgesic effectiveness with improved safety.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpain.2023.1281698","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T02:18:26Z","timestamp":1696990706000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Role of mu opioid receptor (MOR) agonist efficacy as a determinant of opioid antinociception in a novel assay of pain-depressed behavior in female and male mice"],"prefix":"10.3389","volume":"4","author":[{"given":"S. Stevens","family":"Negus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid I.","family":"Akbarali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minho","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young K.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel A.","family":"Marsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edna J.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"B1","first-page":"1121","article-title":"Characterization of opioid agonist efficacy in a C6 glioma cell line expressing the mu opioid receptor","volume":"278","author":"Emmerson","year":"1996","journal-title":"J Pharmacol Exp Ther"},{"key":"B2","first-page":"496","article-title":"Signal transduction correlates of mu opioid agonist intrinsic efficacy: receptor-stimulated [35S]GTP gamma S binding in mMOR-CHO cells and rat thalamus","volume":"285","author":"Selley","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"B3","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1124\/mol.119.119214","article-title":"Intrinsic efficacy of opioid ligands and its importance for apparent bias, operational analysis, and therapeutic window","volume":"98","author":"Gillis","year":"2020","journal-title":"Mol Pharmacol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/bs.pmbts.2022.06.017","article-title":"Opioid signaling and design of analgesics","volume":"195","author":"Paul","year":"2023","journal-title":"Prog Mol Biol Transl Sci"},{"key":"B5","article-title":"Opioids, analgesia, and pain management","volume-title":"Goodman and gilman\u2019s: The pharmacological basis of therapeutics","author":"Yaksh","year":"2018"},{"key":"B6","volume-title":"Buprenorphine: combatting drug abuse with a unique opioid","author":"Cowan","year":"1995"},{"key":"B7","doi-asserted-by":"publisher","first-page":"661","DOI":"10.2165\/00003088-200544070-00001","article-title":"Buprenorphine: clinical pharmacokinetics in the treatment of opioid dependence","volume":"44","author":"Elkader","year":"2005","journal-title":"Clin Pharmacokinet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"859","DOI":"10.2147\/JPR.S85951","article-title":"Buprenorphine\u2014an attractive opioid with underutilized potential in treatment of chronic pain","volume":"8","author":"Khanna","year":"2015","journal-title":"J Pain Res"},{"key":"B9","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/0376-8716(85)90066-3","article-title":"Nalbuphine","volume":"14","author":"Schmidt","year":"1985","journal-title":"Drug Alcohol Depend"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1016\/0024-3205(89)90273-7","article-title":"Opioid-like discriminative stimulus properties of benzomorphans in the pigeon: stereospecificity and differential substitution patterns","volume":"45","author":"Picker","year":"1989","journal-title":"Life Sci"},{"key":"B11","first-page":"184","article-title":"Drug discrimination in human postaddicts: agonist-antagonist opioids","volume":"250","author":"Preston","year":"1989","journal-title":"J Pharmacol Exp Ther"},{"key":"B12","first-page":"1044","article-title":"Nalbuphine, a mixed kappa 1 and kappa 3 analgesic in mice","volume":"262","author":"Pick","year":"1992","journal-title":"J Pharmacol Exp Ther"},{"key":"B13","first-page":"827","article-title":"Opioid efficacy in a C6 glioma cell line stably expressing the human kappa opioid receptor","volume":"288","author":"Remmers","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"key":"B14","first-page":"259","article-title":"Kappa-opioid receptor effects of butorphanol in rhesus monkeys","volume":"290","author":"Vivian","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"key":"B15","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1124\/pr.118.017210","article-title":"Core outcome measures in preclinical assessment of candidate analgesics","volume":"71","author":"Negus","year":"2019","journal-title":"Pharmacol Rev"},{"key":"B16","first-page":"129","article-title":"Pain assessment: global use of the brief pain inventory","volume":"23","author":"Cleeland","year":"1994","journal-title":"Ann Acad Med Singap"},{"key":"B17","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.pain.2004.09.012","article-title":"Core outcome measures for chronic pain clinical trials: iMMPACT recommendations","volume":"113","author":"Dworkin","year":"2005","journal-title":"Pain"},{"key":"B18","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.jpain.2006.01.447","article-title":"Targeting pain-suppressed behaviors in preclinical assays of pain and analgesia: effects of morphine on acetic acid-suppressed feeding in C57BL\/6J mice","volume":"7","author":"Stevenson","year":"2006","journal-title":"J Pain"},{"key":"B19","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1016\/j.pain.2012.01.016","article-title":"Inflammation-induced decrease in voluntary wheel running in mice: a nonreflexive test for evaluating inflammatory pain and analgesia","volume":"153","author":"Cobos","year":"2012","journal-title":"Pain"},{"key":"B20","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1038\/laban.255","article-title":"Expression and treatment of pain-related behavioral depression","volume":"42","author":"Negus","year":"2013","journal-title":"Lab Anim (NY)"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1097\/j.pain.0000000000001199","article-title":"Evaluation of different drug classes on transient sciatic nerve injury-depressed marble burying in mice","volume":"159","author":"Wilkerson","year":"2018","journal-title":"Pain"},{"key":"B22","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1007\/s12576-019-00693-6","article-title":"Peripheral nerve injury in rats induces alternations in choice behavior associated with food reinforcement","volume":"69","author":"Hayashida","year":"2019","journal-title":"J Physiol Sci"},{"key":"B23","doi-asserted-by":"publisher","first-page":"673940","DOI":"10.3389\/fpain.2021.673940","article-title":"Effects of ketoprofen and morphine on pain-related depression of nestlet shredding in male and female mice","volume":"2","author":"Garner","year":"2021","journal-title":"Front Pain Res (Lausanne)"},{"key":"B24","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1097\/FBP.0000000000000596","article-title":"\u201cReinventing the wheel\u201d to advance the development of pain therapeutics","volume":"32","author":"Kandasamy","year":"2021","journal-title":"Behav Pharmacol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1097\/j.pain.0000000000002127","article-title":"Cage-lid hanging behavior as a translationally relevant measure of pain in mice","volume":"162","author":"Zhang","year":"2021","journal-title":"Pain"},{"key":"B26","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.tips.2018.02.002","article-title":"Addressing the opioid crisis: the importance of choosing translational endpoints in analgesic drug discovery","volume":"39","author":"Negus","year":"2018","journal-title":"Trends Pharmacol Sci"},{"key":"B27","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1007\/s00213-021-06048-7","article-title":"Acute pain-related depression of operant responding maintained by social interaction or food in male and female rats","volume":"239","author":"Baldwin","year":"2022","journal-title":"Psychopharmacology (Berl)"},{"key":"B28","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1124\/jpet.114.219873","article-title":"Effects of mu-opioid receptor agonists in assays of acute pain-stimulated and pain-depressed behavior in male rats: role of mu-agonist efficacy and noxious stimulus intensity","volume":"352","author":"Altarifi","year":"2015","journal-title":"J Pharmacol Exp Ther"},{"key":"B29","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/S0079-6123(08)61085-7","article-title":"Tissue acidosis in nociception and pain","volume":"113","author":"Reeh","year":"1996","journal-title":"Prog Brain Res"},{"key":"B30","first-page":"693","article-title":"Acid-sensing ion channels: a new target for pain and CNS diseases","volume":"12","author":"Sluka","year":"2009","journal-title":"Curr Opin Drug Discov Devel"},{"key":"B31","doi-asserted-by":"publisher","first-page":"5045","DOI":"10.1016\/j.bmcl.2013.07.043","article-title":"Structure activity relationship studies of 17-cyclopropylmethyl-3,14beta-dihydroxy-4,5alpha-epoxy-6alpha-(isoquinoline-3\u2032-carboxamido)morphinan (NAQ) analogues as potent opioid receptor ligands: preliminary results on the role of electronic characteristics for affinity and function","volume":"23","author":"Yuan","year":"2013","journal-title":"Bioorg Med Chem Lett"},{"key":"B32","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1124\/jpet.121.001045","article-title":"Role of efficacy as a determinant of locomotor activation by mu opioid receptor ligands in female and male mice","volume":"382","author":"Santos","year":"2022","journal-title":"J Pharmacol Exp Ther"},{"key":"B33","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1124\/jpet.120.000349","article-title":"Manipulating pharmacodynamic efficacy with agonist+antagonist mixtures: in vitro and in vivo studies with opioids and cannabinoids","volume":"376","author":"Selley","year":"2021","journal-title":"J Pharmacol Exp Ther"},{"key":"B34","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/S0163-1047(84)90569-7","article-title":"Behavioral conditioned responses across multiple conditioning\/testing trials elicited by lithium- and amphetamine-paired flavors","volume":"41","author":"Parker","year":"1984","journal-title":"Behav Neural Biol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.neuropharm.2015.11.024","article-title":"Expression and pharmacological modulation of visceral pain-induced conditioned place aversion in mice","volume":"102","author":"Bagdas","year":"2016","journal-title":"Neuropharmacology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1007\/s00213-022-06093-w","article-title":"Opioid-like adverse effects of tianeptine in male rats and mice","volume":"239","author":"Baird","year":"2022","journal-title":"Psychopharmacology (Berl)"},{"key":"B37","doi-asserted-by":"publisher","first-page":"114805","DOI":"10.1016\/j.bcp.2021.114805","article-title":"Respiratory depressant effects of fentanyl analogs are opioid receptor-mediated","volume":"195","author":"Varshneya","year":"2022","journal-title":"Biochem Pharmacol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1124\/jpet.108.143438","article-title":"Morphine tolerance in the mouse ileum and colon","volume":"327","author":"Ross","year":"2008","journal-title":"J Pharmacol Exp Ther"},{"key":"B39","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1111\/bph.14860","article-title":"Fentanyl depression of respiration: comparison with heroin and morphine","volume":"177","author":"Hill","year":"2020","journal-title":"Br J Pharmacol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1038\/npp.2015.201","article-title":"Ethanol reversal of tolerance to the respiratory depressant effects of morphine","volume":"41","author":"Hill","year":"2016","journal-title":"Neuropsychopharmacology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"107101","DOI":"10.1016\/j.vascn.2021.107101","article-title":"The use of hypercapnic conditions to assess opioid-induced respiratory depression in rats","volume":"111","author":"Crowley","year":"2021","journal-title":"J Pharmacol Toxicol Methods"},{"key":"B42","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1038\/s41386-019-0458-9","article-title":"Experimental design and analysis for consideration of sex as a biological variable","volume":"44","author":"Diester","year":"2019","journal-title":"Neuropsychopharmacol"},{"key":"B43","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences","volume":"39","author":"Faul","year":"2007","journal-title":"Behav. Res. Methods"},{"key":"B44","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1124\/jpet.117.246439","article-title":"Application of receptor theory to the design and use of fixed-proportion mu-opioid agonist and antagonist mixtures in rhesus monkeys","volume":"365","author":"Cornelissen","year":"2018","journal-title":"J Pharmacol Exp Ther"},{"key":"B45","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.neuropharm.2019.01.020","article-title":"Effectiveness comparisons of G-protein biased and unbiased mu opioid receptor ligands in warm water tail-withdrawal and drug discrimination in male and female rats","volume":"150","author":"Schwienteck","year":"2019","journal-title":"Neuropharmacology"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1150236","DOI":"10.3389\/fpain.2023.1150236","article-title":"Climbing behavior by mice as an endpoint for preclinical assessment of drug effects in the absence and presence of pain","volume":"4","author":"Santos","year":"2023","journal-title":"Front Pain Res (Lausanne)"},{"key":"B47","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1124\/jpet.120.000464","article-title":"Behavioral battery for testing candidate analgesics in mice. I. Validation with positive and negative controls","volume":"377","author":"Diester","year":"2021","journal-title":"J Pharmacol Exp Ther"},{"key":"B48","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.lfs.2009.06.006","article-title":"Targeting pain-depressed behaviors in preclinical assays of pain and analgesia: drug effects on acetic acid-depressed locomotor activity in ICR mice","volume":"85","author":"Stevenson","year":"2009","journal-title":"Life Sci"},{"key":"B49","doi-asserted-by":"publisher","first-page":"20190291","DOI":"10.1098\/rstb.2019.0291","article-title":"Evolution of acid nociception: ion channels and receptors for detecting acid","volume":"374","author":"Pattison","year":"2019","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"B50","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.tins.2022.12.007","article-title":"Persistent nociceptor hyperactivity as a painful evolutionary adaptation","volume":"46","author":"Walters","year":"2023","journal-title":"Trends Neurosci"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1097\/j.pain.0000000000000171","article-title":"Effects of ketoprofen, morphine, and kappa opioids on pain-related depression of nesting in mice","volume":"156","author":"Negus","year":"2015","journal-title":"Pain"},{"key":"B52","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/s00213-009-1770-6","article-title":"Effects of kappa opioids in an assay of pain-depressed intracranial self-stimulation in rats","volume":"210","author":"Negus","year":"2010","journal-title":"Psychopharmacology (Berl)"},{"key":"B53","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1097\/FBP.0000000000000198","article-title":"Sex differences and serotonergic mechanisms in the behavioural effects of psilocin","volume":"27","author":"Tyls","year":"2016","journal-title":"Behav Pharmacol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.1007\/s00213-017-4615-8","article-title":"Abuse-related effects of subtype-selective GABA(A) receptor positive allosteric modulators in an assay of intracranial self-stimulation in rats","volume":"234","author":"Schwienteck","year":"2017","journal-title":"Psychopharmacology (Berl)"},{"key":"B55","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1037\/pha0000253","article-title":"Effects of acute and repeated treatment with serotonin 5-HT2A receptor agonist hallucinogens on intracranial self-stimulation in rats","volume":"27","author":"Sakloth","year":"2019","journal-title":"Exp Clin Psychopharmacol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1124\/jpet.121.000497","article-title":"Behavioral battery for testing candidate analgesics in mice. II. Effects of endocannabinoid catabolic enzyme inhibitors and \u03949-tetrahydrocannabinol","volume":"377","author":"Diester","year":"2021","journal-title":"J Pharmacol Exp Ther"},{"key":"B57","doi-asserted-by":"publisher","first-page":"e01111","DOI":"10.1002\/prp2.1111","article-title":"Role of efficacy as a determinant of locomotor activation by mu-opioid receptor (MOR) ligands in female and male mice. II. Effects of novel MOR-selective phenylmorphans with high-to-low MOR efficacy","volume":"11","author":"Santos","year":"2023","journal-title":"Pharmacol Res Perspect"},{"key":"B58","first-page":"466","article-title":"Inhibition of the spontaneous climbing behavior elicited in mice by opiates","volume":"227","author":"Marcais-Collado","year":"1983","journal-title":"J Pharmacol Exp Ther"},{"key":"B59","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1007\/s00213-014-3719-7","article-title":"Effects of the novel, selective and low-efficacy mu opioid receptor ligand NAQ on intracranial self-stimulation in rats","volume":"232","author":"Altarifi","year":"2015","journal-title":"Psychopharmacology (Berl)"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1021\/acsptsci.2c00178","article-title":"Preclinical characterization and development on NAQ as a mu opioid receptor partial agonist for opioid use disorder treatment","volume":"5","author":"Pagare","year":"2022","journal-title":"ACS Pharmacol Transl Sci"},{"key":"B61","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1097\/FBP.0b013e328358593c","article-title":"Role of micro-opioid receptor reserve and micro-agonist efficacy as determinants of the effects of micro-agonists on intracranial self-stimulation in rats","volume":"23","author":"Altarifi","year":"2012","journal-title":"Behav Pharmacol"},{"key":"B62","doi-asserted-by":"publisher","first-page":"107689","DOI":"10.1016\/j.neuropharm.2019.107689","article-title":"Interactions between pain states and opioid reward assessed with intracranial self-stimulation in rats","volume":"160","author":"Moerke","year":"2019","journal-title":"Neuropharmacology"},{"key":"B63","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.neuropharm.2019.03.020","article-title":"Role of agonist efficacy in exposure-induced enhancement of mu opioid reward in rats","volume":"151","author":"Moerke","year":"2019","journal-title":"Neuropharmacology"},{"key":"B64","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.drugalcdep.2012.10.026","article-title":"Role of phenmetrazine as an active metabolite of phendimetrazine: evidence from studies of drug discrimination and pharmacokinetics in rhesus monkeys","volume":"130","author":"Banks","year":"2013","journal-title":"Drug Alcohol Depend"},{"key":"B65","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1007\/7854_2016_36","article-title":"Pharmacokinetic-pharmacodynamic (PKPD) analysis with drug discrimination","volume":"39","author":"Negus","year":"2018","journal-title":"Curr Top Behav Neurosci"}],"container-title":["Frontiers in Pain Research"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpain.2023.1281698\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T02:18:35Z","timestamp":1696990715000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpain.2023.1281698\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,11]]},"references-count":65,"alternative-id":["10.3389\/fpain.2023.1281698"],"URL":"https:\/\/doi.org\/10.3389\/fpain.2023.1281698","relation":{},"ISSN":["2673-561X"],"issn-type":[{"value":"2673-561X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,11]]},"article-number":"1281698"}}