{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T21:53:34Z","timestamp":1788731614116,"version":"build-2803163510"},"reference-count":61,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T00:00:00Z","timestamp":1670803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universidad de Buenos Aires Ciencia y Tecnolog\u00eda (UBACYT)","award":["20020130100666BA"],"award-info":[{"award-number":["20020130100666BA"]}]},{"name":"Universidad de Buenos Aires Ciencia y Tecnolog\u00eda (UBACYT)","award":["01\/Q666"],"award-info":[{"award-number":["01\/Q666"]}]},{"name":"Universidad de Buenos Aires Ciencia y Tecnolog\u00eda (UBACYT)","award":["IIR-AR-002659"],"award-info":[{"award-number":["IIR-AR-002659"]}]},{"name":"University of Buenos Aires","award":["20020130100666BA"],"award-info":[{"award-number":["20020130100666BA"]}]},{"name":"University of Buenos Aires","award":["01\/Q666"],"award-info":[{"award-number":["01\/Q666"]}]},{"name":"University of Buenos Aires","award":["IIR-AR-002659"],"award-info":[{"award-number":["IIR-AR-002659"]}]},{"name":"Takeda Pharmaceuticals International AG Singapore Branch","award":["20020130100666BA"],"award-info":[{"award-number":["20020130100666BA"]}]},{"name":"Takeda Pharmaceuticals International AG Singapore Branch","award":["01\/Q666"],"award-info":[{"award-number":["01\/Q666"]}]},{"name":"Takeda Pharmaceuticals International AG Singapore Branch","award":["IIR-AR-002659"],"award-info":[{"award-number":["IIR-AR-002659"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Hindpaw injection of formalin in rodents is used to assess acute persistent pain. The response to formalin is biphasic. The initial response (first minutes) is thought to be linked to inflammatory, peripheral mechanisms, while the latter (around 30 min after the injection), is linked to central mechanisms. This model is useful to analyze the effect of drugs at one or both phases, and the involvement of ion channels in the response. Acid-sensing ion channels (ASICs) regulate synaptic activities and play important roles in pain conditions. Recently, psalmotoxin-1 (Pctx-1), a toxin that inhibits ASIC1a-constituted channels, and antisense ASIC1a-RNA, intrathecal administered in mice were shown to affect both phases of the test. Methods: The mouse formalin test was performed on C57\/BL6 7- to 9-week-old mice. Behavioral tests were conducted and tissue was extracted to detect proteins (ASIC1 and pERK) and ASIC1-mRNA and mir485-5p levels. Results: The injection of formalin was accompanied by an increase in ASIC1 levels. This was detected at the contralateral anterior cingulate cortex (ACC) compared to the ipsilateral side, and both sides of the ACC of vehicle-injected animals. At the spinal cord and dorsal root ganglia, ASIC1 levels followed a gradient stronger at lumbar (L) 3 and decreased towards L5. Gender differences were detected at the ACC; with female mice showing higher ASIC1a levels at the ACC. No significant changes in ASIC1-mRNA levels were detected. Evidence suggests ASIC1 upregulation depends on regulatory microRNAs. Conclusion: This work highlights the important role of ASIC1 in pain and the potential role of pharmacological therapies aimed at this channel.<\/jats:p>","DOI":"10.3390\/ph15121539","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T04:34:20Z","timestamp":1670819660000},"page":"1539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Segmental Upregulation of ASIC1 Channels in the Formalin Acute Pain Mouse Model"],"prefix":"10.3390","volume":"15","author":[{"given":"Mar\u00eda Natalia","family":"Gobetto","sequence":"first","affiliation":[{"name":"Instituto de Fisiolog\u00eda Biologia Moleculary Neurociencias-IFIBYNE-UBA-CONICET, LFBM, Bueno Aires CP1428, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6809-286X","authenticated-orcid":false,"given":"Libia Catalina Salinas","family":"Castellanos","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Biologia Moleculary Neurociencias-IFIBYNE-UBA-CONICET, LFBM, Bueno Aires CP1428, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia Estefan\u00eda","family":"Contreras","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Biologia Moleculary Neurociencias-IFIBYNE-UBA-CONICET, LFBM, Bueno Aires CP1428, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5159-218X","authenticated-orcid":false,"given":"Alejandro Omar","family":"Sodero","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research (BIOMED), Pontifical Catholic University of Argentina (UCA) and National Scientific and Technical Research Council (CONICET), Buenos Aires C1107AFF, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dami\u00e1n Alejandro","family":"Cambiagno","sequence":"additional","affiliation":[{"name":"Unidad de Estudios Agropecuarios (UDEA), INTA-CONICET, C\u00f3rdoba X5020ICA, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina Oriana Mingolo","family":"Malnati","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Biologia Moleculary Neurociencias-IFIBYNE-UBA-CONICET, LFBM, Bueno Aires CP1428, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayra Micaela","family":"Montes","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Biologia Moleculary Neurociencias-IFIBYNE-UBA-CONICET, LFBM, Bueno Aires CP1428, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osvaldo Daniel","family":"Uchitel","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Biologia Moleculary Neurociencias-IFIBYNE-UBA-CONICET, LFBM, Bueno Aires CP1428, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Weissmann","sequence":"additional","affiliation":[{"name":"Instituto de Fisiolog\u00eda Biologia Moleculary Neurociencias-IFIBYNE-UBA-CONICET, LFBM, Bueno Aires CP1428, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.1111\/bph.13533","article-title":"The function and regulation of acid-sensing ion channels (ASICs) and the epithelial Na + channel (ENaC): IUPHAR Review 19","volume":"173","author":"Boscardin","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e22120","DOI":"10.1002\/syn.22120","article-title":"Synaptic signals mediated by protons and acid-sensing ion channels","volume":"73","author":"Uchitel","year":"2019","journal-title":"Synapse"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1113\/JP278707","article-title":"Coupling structure with function in acid-sensing ion channels: Challenges in pursuit of proton sensors","volume":"599","author":"Rook","year":"2021","journal-title":"J. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17325","DOI":"10.1074\/jbc.R700011200","article-title":"Acid-sensing Ion Channels in Sensory Perception","volume":"282","author":"Lingueglia","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11139","DOI":"10.1523\/JNEUROSCI.3364-07.2007","article-title":"Upregulation of acid-sensing ion channel ASIC1a in spinal dorsal horn neurons contributes to inflammatory pain hypersensitivity","volume":"27","author":"Duan","year":"2007","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3389\/fncel.2020.00103","article-title":"Differential Expression of Acid\u2014Sensing Ion Channels in Mouse Primary Afferents in Na\u00efve and Injured Conditions","volume":"14","author":"Labrecque","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"E7469","DOI":"10.1073\/pnas.1807233115","article-title":"Selection of an ASIC1a-blocking combinatorial antibody that protects cells from ischemic death","volume":"115","author":"Qiang","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"NS20190099","DOI":"10.1042\/NS20190099","article-title":"Non-coding RNAs in neuropathic pain","volume":"4","author":"Kalpachidou","year":"2020","journal-title":"Neuronal Signal."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1080\/14728222.2019.1550075","article-title":"Long noncoding RNA (lncRNA): A target in neuropathic pain","volume":"23","author":"Wu","year":"2019","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.molmed.2014.05.006","article-title":"Noncoding RNAs: Key molecules in understanding and treating pain","volume":"20","author":"Bali","year":"2014","journal-title":"Trends Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3013","DOI":"10.2147\/JPR.S279902","article-title":"Decreased mir-485-5p contributes to inflammatory pain through post-transcriptional upregulation of asic1 in rat dorsal root ganglion","volume":"13","author":"Xu","year":"2020","journal-title":"J. Pain Res."},{"key":"ref_12","first-page":"51","article-title":"Peripheral and spinal TRPA1 channels contribute to formalin-induced long-lasting mechanical hypersensitivity","volume":"11","year":"2018","journal-title":"J. Pain Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"113446","DOI":"10.1016\/j.bbr.2021.113446","article-title":"TREK-1 potassium channels participate in acute and long-lasting nociceptive hypersensitivity induced by formalin in rats","volume":"413","year":"2021","journal-title":"Behav. Brain Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1211\/jpp.58.4.0008","article-title":"Participation of the spinal TRPV1 receptors in formalin-evoked pain transduction: A study using a selective TRPV1 antagonist, iodo-resiniferatoxin","volume":"58","author":"Kanai","year":"2010","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/S0024-3205(99)00336-7","article-title":"Antinociception produced by systemic, spinal and supraspinal administration of amiloride in mice","volume":"65","author":"Ferreira","year":"1999","journal-title":"Life Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.3346\/jkms.2013.28.8.1238","article-title":"Antinociceptive effects of amiloride and benzamil in neuropathic pain model rats","volume":"28","author":"Jeong","year":"2013","journal-title":"J. Korean Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/nn1940","article-title":"A tarantula peptide against pain via ASIC1a channels and opioid mechanisms","volume":"10","author":"Mazzuca","year":"2007","journal-title":"Nat. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"104824","DOI":"10.1016\/j.neuint.2020.104824","article-title":"Upregulation of ASIC1a channels in an in vitro model of Fabry disease","volume":"140","author":"Salinas","year":"2020","journal-title":"Neurochem. Int."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"735414","DOI":"10.3389\/fncel.2021.735414","article-title":"Signaling Pathways in Proton and Non-proton ASIC1a Activation","volume":"15","author":"Uchitel","year":"2021","journal-title":"Front. Cell. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/16040","article-title":"Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity","volume":"2","author":"Ji","year":"1999","journal-title":"Nat. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6153215","DOI":"10.1155\/2016\/6153215","article-title":"MAPK Pathways Are Involved in Neuropathic Pain in Rats with Chronic Compression of the Dorsal Root Ganglion","volume":"2016","author":"Qu","year":"2016","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1517\/14728222.9.4.699","article-title":"The ERK\/MAPK pathway, as a target for the treatment of neuropathic pain","volume":"9","author":"Ma","year":"2005","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1097\/ALN.0b013e3182242045","article-title":"Biphasic activation of extracellular signal-regulated kinase in anterior cingulate cortex distinctly regulates the development of pain-related anxiety and mechanical hypersensitivity in rats after incision","volume":"115","author":"Dai","year":"2011","journal-title":"Anesthesiology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1744-8069-4-28","article-title":"Activation of Erk in the anterior cingulate cortex during the induction and expression of chronic pain","volume":"4","author":"Wei","year":"2008","journal-title":"Mol. Pain"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1523\/JNEUROSCI.4300-08.2009","article-title":"Activation of extracellular signal-regulated kinase in the anterior cingulate cortex contributes to the induction and expression of affective pain","volume":"29","author":"Cao","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.neuroscience.2020.07.013","article-title":"Antinociceptive Effects of the GPR55 Antagonist CID16020046 Injected into the Rat Anterior Cingulate Cortex","volume":"443","author":"Okine","year":"2020","journal-title":"Neuroscience"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1080\/19336950.2015.1075105","article-title":"Ion channel therapeutics for pain","volume":"9","author":"Skerratt","year":"2015","journal-title":"Channels"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"102030","DOI":"10.1016\/j.pneurobio.2021.102030","article-title":"Neuropathic pain modeling: Focus on synaptic and ion channel mechanisms","volume":"201","author":"Landry","year":"2021","journal-title":"Prog. Neurobiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2174\/1568010043483980","article-title":"Acid-sensing ion channels (ASICs): New targets for the analgesic effects of non-steroid anti-inflammatory drugs (NSAIDs)","volume":"3","author":"Voilley","year":"2004","journal-title":"Curr. Drug Targets Inflamm. Allergy"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e279","DOI":"10.1038\/oncsis.2016.81","article-title":"ERK-mediated NF-\u03baB activation through ASIC1 in response to acidosis","volume":"5","author":"Chen","year":"2016","journal-title":"Oncogenesis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"F531","DOI":"10.1152\/ajprenal.00546.2019","article-title":"Acid-sensing ion channels in sensory signaling","volume":"318","author":"Carattino","year":"2020","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.ejpain.2008.07.001","article-title":"Mice lacking acid-sensing ion channels (ASIC) 1 or 2, but not ASIC3, show increased pain behaviour in the formalin test","volume":"13","author":"Staniland","year":"2009","journal-title":"Eur. J. Pain"},{"key":"ref_33","first-page":"404","article-title":"Mediating roles of the vanilloid receptor TRPV1 in activation of rat primary afferent nociceptive neurons by formaldehyde","volume":"61","author":"Tian","year":"2009","journal-title":"Sheng Li Xue Bao"},{"key":"ref_34","first-page":"136","article-title":"Antinociceptive actions of spinal nonsteroidal anti-inflammatory agents on the formalin test in the rat","volume":"263","author":"Malmberg","year":"1992","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8026","DOI":"10.1523\/JNEUROSCI.21-20-08026.2001","article-title":"Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors","volume":"21","author":"Voilley","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.pain.2008.01.016","article-title":"Species and strain differences in rodent sciatic nerve anatomy: Implications for studies of neuropathic pain","volume":"136","author":"Rigaud","year":"2008","journal-title":"Pain"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1186\/s12974-018-1222-5","article-title":"Molecular and cellular identification of the immune response in peripheral ganglia following nerve injury","volume":"15","author":"Lindborg","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"12642","DOI":"10.1038\/s41598-017-12879-2","article-title":"Time-lapse imaging of microRNA activity reveals the kinetics of microRNA activation in single living cells","volume":"7","author":"Ando","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5689","DOI":"10.4049\/jimmunol.180.8.5689","article-title":"Rapid changes in microRNA-146a expression negatively regulate the interleukin-1\u03b2 induced inflammatory response in human lung alveolar epithelial cells","volume":"180","author":"Perry","year":"2008","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.pain.2012.11.010","article-title":"Modulation of central nervous system-specific microRNA-124a alters the inflammatory response in the formalin test in mice","volume":"154","author":"Kynast","year":"2013","journal-title":"Pain"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.3324\/haematol.2018.205047","article-title":"Impaired microRNA processing in neutrophils from rheumatoid arthritis patients confers their pathogenic profile. Modulation by biological therapies","volume":"105","author":"Cecchi","year":"2020","journal-title":"Haematologica"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/j.omtn.2020.04.002","article-title":"The Interplay among miRNAs, Major Cytokines, and Cancer-Related Inflammation","volume":"20","author":"Chakraborty","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.7150\/ijbs.41641","article-title":"Inflammation-dependent downregulation of miR-532-3p mediates apoptotic signaling in human sarcopenia through targeting BAK1","volume":"16","author":"Chen","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"15113","DOI":"10.1523\/JNEUROSCI.3947-10.2010","article-title":"IL-6- and NGF-induced rapid control of protein synthesis and nociceptive plasticity via convergent signaling to the eIF4F complex","volume":"30","author":"Melemedjian","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1007\/s12035-018-1245-z","article-title":"Pain-Relieving Effects of mTOR Inhibitor in the Anterior Cingulate Cortex of Neuropathic Rats","volume":"56","author":"Um","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0006-8993(02)03661-2","article-title":"The role of sex hormones on formalin-induced nociceptive responses","volume":"958","author":"Gaumond","year":"2002","journal-title":"Brain Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0006-8993(99)01353-0","article-title":"Sex differences in late behavioral response to subcutaneous formalin injection in mice","volume":"829","author":"Kim","year":"1999","journal-title":"Brain Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/S0024-3205(02)02344-5","article-title":"Tonic pain response in mice: Effects of sex, season and time of day","volume":"72","author":"Perissin","year":"2003","journal-title":"Life Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1152\/ajpregu.00902.2005","article-title":"Sex differences in the effects of amiloride on formalin test nociception in mice","volume":"291","author":"Chanda","year":"2006","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.gpb.2018.03.004","article-title":"Identification and Analysis of Human Sex-biased MicroRNAs","volume":"16","author":"Cui","year":"2018","journal-title":"Genomics. Proteom. Bioinform."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"39812","DOI":"10.1038\/srep39812","article-title":"miRNA and mRNA expression analysis reveals potential sex-biased miRNA expression","volume":"7","author":"Guo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/2042-6410-5-3","article-title":"Influence of sex differences on microRNA gene regulation in disease","volume":"5","author":"Sharma","year":"2014","journal-title":"Biol. Sex Differ."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.brainres.2011.01.002","article-title":"Role of different brain areas in peripheral nerve injury-induced neuropathic pain","volume":"1381","author":"Jaggi","year":"2011","journal-title":"Brain Res."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Chen, T., Koga, K., Descalzi, G., Qiu, S., Wang, J., Zhang, L.S., Zhang, Z.J., He, X.B., Qin, X., and Xu, F.Q. (2014). Postsynaptic potentiation of corticospinal projecting neurons in the anterior cingulate cortex after nerve injury. Mol. Pain, 10.","DOI":"10.1186\/1744-8069-10-33"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3389\/fncel.2018.00107","article-title":"Neuropathic Pain Causes Pyramidal Neuronal Hyperactivity in the Anterior Cingulate Cortex","volume":"12","author":"Zhao","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3346\/jkms.2002.17.1.81","article-title":"Effects of different concentrations of formalin on paw edema and pain behaviors in rats","volume":"17","author":"Lee","year":"2002","journal-title":"J. Korean Med. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ejphar.2009.01.004","article-title":"Pharmacological assessment of the rat formalin test utilizing the clinically used analgesic drugs gabapentin, lamotrigine, morphine, duloxetine, tramadol and ibuprofen: Influence of low and high formalin concentrations","volume":"605","author":"Munro","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"9988","DOI":"10.1523\/JNEUROSCI.0881-21.2021","article-title":"Contralateral Projection of Anterior Cingulate Cortex Contributes to Mirror-Image Pain","volume":"41","author":"Hu","year":"2021","journal-title":"J. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"891","DOI":"10.12688\/f1000research.18338.1","article-title":"A refinement to the formalin test in mice [version 2; peer review: 2 approved]","volume":"8","author":"Lopes","year":"2019","journal-title":"F1000Research"},{"key":"ref_60","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":"ref_61","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.neuroscience.2021.09.017","article-title":"SIRT-1 Activity Sustains Cholesterol Synthesis in the Brain","volume":"476","author":"Paulazo","year":"2021","journal-title":"Neuroscience"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/12\/1539\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:39:38Z","timestamp":1760146778000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/12\/1539"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,12]]},"references-count":61,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ph15121539"],"URL":"https:\/\/doi.org\/10.3390\/ph15121539","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,12]]}}}