{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T04:29:50Z","timestamp":1784003390436,"version":"3.55.0"},"reference-count":89,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T00:00:00Z","timestamp":1673827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universitat de Girona","award":["2014-DI-026 ESTEVE"],"award-info":[{"award-number":["2014-DI-026 ESTEVE"]}]},{"name":"Universitat de Girona","award":["201705.30.31"],"award-info":[{"award-number":["201705.30.31"]}]},{"name":"La Marat\u00f3 de TV3 Foundation","award":["2014-DI-026 ESTEVE"],"award-info":[{"award-number":["2014-DI-026 ESTEVE"]}]},{"name":"La Marat\u00f3 de TV3 Foundation","award":["201705.30.31"],"award-info":[{"award-number":["201705.30.31"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Central neuropathic pain is not only characterized by reflexive pain responses, but also emotional or affective nonreflexive pain responses, especially in women. Some pieces of evidence suggest that the activation of the neuroimmune system may be contributing to the manifestation of mood disorders in patients with chronic pain conditions, but the mechanisms that contribute to the development and chronicity of CNP and its associated disorders remain poorly understood. This study aimed to determine whether neuroinflammatory factor over-expression in the spinal cord and supraspinal structures may be associated with reflexive and nonreflexive pain response development from acute SCI phase to 12 weeks post-injury in female mice. The results show that transient reflexive responses were observed during the SCI acute phase associated with transient cytokine overexpression in the spinal cord. In contrast, increased nonreflexive pain responses were observed in the chronic phase associated with cytokine overexpression in supraspinal structures, especially in mPFC. In addition, results revealed that besides cytokines, the mPFC showed an increased glial activation as well as CX3CL1\/CX3CR1 upregulation in the neurons, suggesting the contribution of neuron-glia crosstalk in the development of nonreflexive pain responses in the chronic spinal cord injury phase.<\/jats:p>","DOI":"10.3390\/ijms24021761","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T03:40:34Z","timestamp":1673840434000},"page":"1761","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Transient Reflexive Pain Responses and Chronic Affective Nonreflexive Pain Responses Associated with Neuroinflammation Processes in Both Spinal and Supraspinal Structures in Spinal Cord-Injured Female Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"S\u00edlvia","family":"Castany","sequence":"first","affiliation":[{"name":"Research Group of Clinical Anatomy, Embryology and Neuroscience (NEOMA), Department of Medical Sciences, University of Girona, 17003 Girona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Bag\u00f3-Mas","sequence":"additional","affiliation":[{"name":"Research Group of Clinical Anatomy, Embryology and Neuroscience (NEOMA), Department of Medical Sciences, University of Girona, 17003 Girona, Catalonia, Spain"},{"name":"Department of Anatomy, Division of Neuroanatomy, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Miguel","family":"Vela","sequence":"additional","affiliation":[{"name":"WeLab Barcelona, Parc Cient\u00edfic de Barcelona, 08028 Barcelona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0816-1146","authenticated-orcid":false,"given":"Enrique","family":"Verd\u00fa","sequence":"additional","affiliation":[{"name":"Research Group of Clinical Anatomy, Embryology and Neuroscience (NEOMA), Department of Medical Sciences, University of Girona, 17003 Girona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Bretov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Division of Neuroanatomy, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktorie","family":"Svobodov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Division of Neuroanatomy, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Dubov\u00fd","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Division of Neuroanatomy, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8497-1207","authenticated-orcid":false,"given":"Pere","family":"Boadas-Vaello","sequence":"additional","affiliation":[{"name":"Research Group of Clinical Anatomy, Embryology and Neuroscience (NEOMA), Department of Medical Sciences, University of Girona, 17003 Girona, Catalonia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/ejp.522","article-title":"Pain prevalence and its determinants after spinal cord injury: A systematic review","volume":"19","author":"Kessels","year":"2015","journal-title":"Eur. J. Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/ejp.905","article-title":"Neuropathic pain prevalence following spinal cord injury: A systematic review and meta-analysis","volume":"21","author":"Burke","year":"2017","journal-title":"Eur. J. Pain."},{"key":"ref_3","unstructured":"National Spinal Cord Injury Statistical Center (2020). Facts and Figures at a Glance, University of Alabama at Birmingham. Available online: https:\/\/www.nscisc.uab.edu\/Public\/Facts%20and%20Figures%202020.pdf."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"30898","DOI":"10.1038\/srep30898","article-title":"Functional Recovery from Neural Stem\/Progenitor Cell Transplantation Combined with Treadmill Training in Mice with Chronic Spinal Cord Injury","volume":"6","author":"Tashiro","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.neulet.2012.03.013","article-title":"Cerebral interactions of pain and reward and their relevance for chronic pain","volume":"520","author":"Becker","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_6","first-page":"525","article-title":"Central neuropathic pain and its relation to the quality of life of a person with a traumatic spinal cord injury","volume":"42","author":"Vall","year":"2006","journal-title":"Rev. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/sj.sc.3102022","article-title":"Impact of spinal cord injury on self-perceived pre- and postmorbid cognitive, emotional and physical functioning","volume":"45","author":"Murray","year":"2007","journal-title":"Spinal Cord."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/j.apmr.2016.11.011","article-title":"Depression in Individuals with Traumatic and Nontraumatic Spinal Cord Injury Living in the Community","volume":"98","author":"Chamarro","year":"2017","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.apmr.2017.06.012","article-title":"Health Conditions: Effect on Function, Health-Related Quality of Life, and Life Satisfaction After Traumatic Spinal Cord Injury. A Prospective Observational Registry Cohort Study","volume":"99","author":"Rivers","year":"2018","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.jpain.2008.12.007","article-title":"Comorbid chronic pain and depression: Who is at risk?","volume":"10","author":"Miller","year":"2009","journal-title":"J. Pain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s11920-013-0421-0","article-title":"Pain and depression: An integrative review of neurobiological and psychological factors","volume":"15","author":"Goesling","year":"2013","journal-title":"Curr. Psychiatry Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.pneurobio.2014.01.003","article-title":"Preclinical research on pain comorbidity with affective disorders and cognitive deficits: Challenges and perspectives","volume":"116","author":"Liu","year":"2014","journal-title":"Prog. Neurobiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.biopsych.2009.09.033","article-title":"A meta-analysis of cytokines in major depression","volume":"67","author":"Dowlati","year":"2010","journal-title":"Biol. Psychiatry."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/da.22084","article-title":"Cytokine targets in the brain: Impact on neurotransmitters and neurocircuits","volume":"30","author":"Miller","year":"2013","journal-title":"Depress. Anxiety"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"963","DOI":"10.2174\/1381612053381701","article-title":"Cytokines as a precipitant of depressive illness: Animal and human studies","volume":"11","author":"Anisman","year":"2005","journal-title":"Curr. Pharm. Des."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s00213-002-1273-1","article-title":"Dissociating anorexia and anhedonia elicited by interleukin-1beta: Antidepressant and gender effects on responding for \"free chow\" and \"earned\" sucrose intake","volume":"165","author":"Merali","year":"2003","journal-title":"Psychopharmacology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jneuroim.2010.08.013","article-title":"The neuro-immune balance in neuropathic pain: Involvement of inflammatory immune cells, immune-like glial cells and cytokines","volume":"229","author":"Austin","year":"2010","journal-title":"J. Neuroimmunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.brainresrev.2008.12.010","article-title":"Mechanisms of Chronic Central Neuropathic Pain after Spinal Cord Injury\u2019","volume":"60","author":"Hulsebosch","year":"2009","journal-title":"Brain Res. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Watson, J.L., Hala, T.J., Putatunda, R., Sannie, D., and Lepore, A.C. (2014). Persistent at-level thermal hyperalgesia and tactile allodynia accompany chronic neuronal and astrocyte activation in superficial dorsal horn following mouse cervical contusion spinal cord injury. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0109099"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12447","DOI":"10.1523\/JNEUROSCI.0846-13.2013","article-title":"TrkB.T1 contributes to neuropathic pain after spinal cord injury through regulation of cell cycle pathways","volume":"33","author":"Wu","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.4161\/cc.29420","article-title":"Isolated spinal cord contusion in rats induces chronic brain neuroinflammation, neurodegeneration, and cognitive impairment. Involvement of cell cycle activation","volume":"13","author":"Wu","year":"2014","journal-title":"Cell Cycle"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"10989","DOI":"10.1523\/JNEUROSCI.5110-13.2014","article-title":"Spinal cord injury causes brain inflammation associated with cognitive and affective changes: Role of cell cycle pathways","volume":"34","author":"Wu","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3698","DOI":"10.1080\/15384101.2015.1104436","article-title":"Ablation of the transcription factors E2F1-2 limits neuroinflammation and associated neurological deficits after contusive spinal cord injury","volume":"14","author":"Wu","year":"2015","journal-title":"Cell Cycle"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1089\/neu.2015.4348","article-title":"Endoplasmic Reticulum Stress and Disrupted Neurogenesis in the Brain Are Associated with Cognitive Impairment and Depressive-Like Behavior after Spinal Cord Injury","volume":"33","author":"Wu","year":"2016","journal-title":"J. Neurotrauma"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1097\/j.pain.0000000000000393","article-title":"Cell cycle inhibition limits development and maintenance of neuropathic pain following spinal cord injury","volume":"157","author":"Wu","year":"2016","journal-title":"Pain"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/s12974-022-02628-2","article-title":"Coexistence of chronic hyperalgesia and multilevel neuroinflammatory responses after experimental SCI: A systematic approach to profiling neuropathic pain","volume":"19","author":"Wang","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.neulet.2016.08.029","article-title":"Nerve injury induced activation of fast-conducting high threshold mechanoreceptors predicts non-reflexive pain related behavior","volume":"632","author":"Boada","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5247","DOI":"10.1523\/JNEUROSCI.3494-14.2015","article-title":"Activation of corticostriatal circuitry relieves chronic neuropathic pain","volume":"35","author":"Lee","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7062","DOI":"10.1038\/ncomms8062","article-title":"Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression","volume":"6","author":"Bagot","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7445","DOI":"10.1523\/JNEUROSCI.1812-08.2008","article-title":"Presynaptic and postsynaptic amplifications of neuropathic pain in the anterior cingulate cortex","volume":"28","author":"Xu","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/1744-8069-9-21","article-title":"Peripheral nerve injury is accompanied by chronic transcriptome-wide changes in the mouse prefrontal cortex","volume":"9","author":"Alvarado","year":"2013","journal-title":"Mol. Pain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.neuron.2010.03.002","article-title":"Predicting value of pain and analgesia: Nucleus accumbens response to noxious stimuli changes in the presence of chronic pain","volume":"66","author":"Baliki","year":"2010","journal-title":"Neuron"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.neuroimage.2010.12.013","article-title":"Contribution of chronic pain and neuroticism to abnormal forebrain gray matter in patients with temporomandibular disorder","volume":"55","author":"Moayedi","year":"2011","journal-title":"NeuroImage"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/nrn3381","article-title":"The brain reward circuitry in mood disorders","volume":"14","author":"Russo","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.pain.2007.12.008","article-title":"Clinical and pre-clinical pain assessment: Are we measuring the same thing?","volume":"135","author":"Vierck","year":"2008","journal-title":"Pain"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/nrn2606","article-title":"Animal models of pain: Progress and challenges","volume":"10","author":"Mogil","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1001\/archpsyc.1981.01780370071010","article-title":"Psychiatric disorders in patients with spinal cord injuries","volume":"38","author":"Fullerton","year":"1981","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_38","first-page":"9","article-title":"Factors predicting depression among persons with spinal cord injury 1 to 5 years post injury","volume":"29","author":"Ketchum","year":"2011","journal-title":"Neuro Rehabil."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1097\/WNP.0b013e31827edb0c","article-title":"Central correlates of impaired information processing in people with spinal cord injury","volume":"30","author":"Lazzaro","year":"2013","journal-title":"J. Clin. Neurophysiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1089\/neu.2013.3204","article-title":"Assessment of depression in a rodent model of spinal cord injury","volume":"31","author":"Luedtke","year":"2014","journal-title":"J. Neurotrauma"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.bbi.2015.08.009","article-title":"Inflammation is increased with anxiety- and depression-like signs in a rat model of spinal cord injury","volume":"51","author":"Peters","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_42","first-page":"2473","article-title":"Assessment of social interaction behaviors","volume":"48","author":"Lipina","year":"2011","journal-title":"J. Vis. Exp."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"13428","DOI":"10.1038\/s41598-017-13987-9","article-title":"Pharmacological sensitivity of reflexive and nonreflexive outcomes as a correlate of the sensory and affective responses to visceral pain in mice","volume":"7","author":"Zamanillo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/ejp.722","article-title":"Epigallocatechin-3-gallate treatment reduces thermal hyperalgesia after spinal cord injury by down-regulating RhoA expression in mice","volume":"20","author":"Homs","year":"2016","journal-title":"Eur. J. Pain."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3389\/fncel.2016.00098","article-title":"Inflammogenesis of Secondary Spinal Cord Injury","volume":"10","author":"Anwar","year":"2016","journal-title":"Front. Cell. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"E2","DOI":"10.3171\/FOC.2008.25.11.E2","article-title":"Current status of acute spinal cord injury pathophysiology and emerging therapies: Promise on the horizon","volume":"25","author":"Rowland","year":"2008","journal-title":"Neurosurg. Focus"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1002\/jnr.22820","article-title":"Expression of inflammatory cytokines following acute spinal cord injury in a rodent model","volume":"90","author":"Stammers","year":"2012","journal-title":"J. Neurosci. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1124\/pr.113.008144","article-title":"Neuroinflammation and comorbidity of pain and depression","volume":"66","author":"Walker","year":"2013","journal-title":"Pharmacol. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nature10360","article-title":"Neocortical excitation\/inhibition balance in information processing and social dysfunction","volume":"477","author":"Yizhar","year":"2011","journal-title":"Nature"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/0304-3959(81)90140-8","article-title":"Depression, anhedonia and anxiety in temporomandibular joint and other facial pain syndromes","volume":"11","author":"Marbach","year":"1981","journal-title":"Pain"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.tins.2016.01.006","article-title":"Neural Mechanisms Underlying Anxiety-Chronic Pain Interactions","volume":"39","author":"Zhuo","year":"2016","journal-title":"Trends Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1046\/j.1471-4159.2002.01071.x","article-title":"Suppression of the morphine-induced rewarding effect in the rat with neuropathic pain: Implication of the reduction in mu-opioid receptor functions in the ventral tegmental area","volume":"82","author":"Ozaki","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.pain.2003.12.015","article-title":"Chronic pain patients are impaired on an emotional decision-making task","volume":"108","author":"Apkarian","year":"2004","journal-title":"Pain"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.neuroscience.2009.04.011","article-title":"Cognitive impairment of prefrontal-dependent decision-making in rats after the onset of chronic pain","volume":"161","author":"Lima","year":"2009","journal-title":"Neuroscience"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1016\/j.pain.2011.02.027","article-title":"Operant learning of perceptual sensitization and habituation is impaired in fibromyalgia patients with and without irritable bowel syndrome","volume":"152","author":"Becker","year":"2011","journal-title":"Pain"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1007\/s12035-018-1130-9","article-title":"Role of the prefrontal cortex in pain processing","volume":"56","author":"Ong","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuroscience.2006.06.027","article-title":"Interactions among the medial prefrontal cortex, hippocampus and midline thalamus in emotional and cognitive processing in the rat","volume":"142","author":"Vertes","year":"2006","journal-title":"Neuroscience"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s00429-012-0493-3","article-title":"Cytoarchitecture of mouse and rat cingulate cortex with human homologies","volume":"219","author":"Vogt","year":"2014","journal-title":"Brain Struct. Funct."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3339","DOI":"10.1523\/JNEUROSCI.4874-09.2010","article-title":"L Neurons in anterior cingulate cortex multiplex information about reward and action","volume":"30","author":"Hayden","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/nrn1704","article-title":"Pain and emotion interactions in subregions of the cingulate gyrus","volume":"6","author":"Vogt","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1016\/j.pain.2013.08.023","article-title":"Astrocytes are involved in long-term facilitation of neuronal excitation in the anterior cingulate cortex of mice with inflammatory pain","volume":"154","author":"Ikeda","year":"2013","journal-title":"Pain"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.neuroscience.2019.08.005","article-title":"Peripheral nerve injury triggers neuroinflammation in the medial prefrontal cortex and ventral hippocampus in a subgroup of rats with coincident affective behavioural changes","volume":"416","author":"Fiore","year":"2019","journal-title":"Neuroscience"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4683","DOI":"10.1523\/JNEUROSCI.2657-12.2013","article-title":"Critical Role of the Astrocyte for Functional Remodeling in Contralateral Hemisphere of Somatosensory Cortex after Stroke","volume":"33","author":"Takatsuru","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.molmed.2017.04.005","article-title":"Should We Stop Saying \u2018Glia\u2019 and \u2018Neuroinflammation\u2019?","volume":"23","author":"Masgrau","year":"2017","journal-title":"Trends Mol. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.bbi.2016.04.012","article-title":"Are the emergence of affective disturbances in neuropathic pain states contingent on supraspinal neuroinflammation?","volume":"56","author":"Fiore","year":"2016","journal-title":"Brain Behav. Immun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.cophys.2019.03.008","article-title":"Supraspinal neuroimmune crosstalk in chronic pain states","volume":"11","author":"Austin","year":"2019","journal-title":"Curr. Opin. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3389\/fncel.2014.00121","article-title":"Fractalkine\/CX3CR1 signaling during neuropathic pain","volume":"8","author":"Clark","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1111\/j.1460-9568.2004.03593.x","article-title":"Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions","volume":"20","author":"Verge","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.pharmthera.2010.01.002","article-title":"Chemokines, neuronal-glial interactions, and central processing of neuropathic pain","volume":"126","author":"Gao","year":"2010","journal-title":"Pharmacol. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.brainresrev.2008.12.002","article-title":"Chemokines and pain mechanisms","volume":"60","author":"Abbadie","year":"2009","journal-title":"Brain Res. Rev."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6945","DOI":"10.1523\/JNEUROSCI.0828-09.2009","article-title":"The liberation of fractalkine in the dorsal horn requires microglial cathepsin S","volume":"29","author":"Clark","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.expneurol.2011.09.012","article-title":"Microglial signalling mechanisms: Cathepsin S and Fractalkine","volume":"234","author":"Clark","year":"2012","journal-title":"Exp. Neurol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3275","DOI":"10.1007\/s00018-017-2513-1","article-title":"Chemokines in neuron-glial cell interaction and pathogenesis of neuropathic pain","volume":"74","author":"Zhang","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.neuroscience.2019.07.035","article-title":"Chemokines: Key Molecules that Orchestrate Communication among Neurons, Microglia and Astrocytes to Preserve Brain Function","volume":"439","author":"Trettel","year":"2020","journal-title":"Neuroscience"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jneuroim.2013.07.020","article-title":"CX3CL1 protects neurons against excitotoxicity enhancing GLT-1 activity on astrocytes","volume":"263","author":"Catalano","year":"2013","journal-title":"J. Neuroimmunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3389\/fncel.2014.00229","article-title":"Modulating neurotoxicity through CX3CL1\/CX3CR1 signaling","volume":"8","author":"Limatola","year":"2014","journal-title":"Front. Cell. Neurosci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"472","DOI":"10.3389\/fncel.2014.00472","article-title":"Fractalkine\/CX3CL1 engages different neuroprotective responses upon selective glutamate receptor overactivation","volume":"8","author":"Lauro","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"222","DOI":"10.3389\/fphar.2019.00222","article-title":"Repeated Sigma-1 Receptor Antagonist MR309 Administration Modulates Central Neuropathic Pain Development After Spinal Cord Injury in Mice","volume":"10","author":"Castany","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3873","DOI":"10.1038\/s41598-018-22217-9","article-title":"Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice","volume":"8","author":"Castany","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"14980","DOI":"10.1038\/s41598-022-19109-4","article-title":"Polyphenolic grape stalk and coffee extracts attenuate spinal cord injury-induced neuropathic pain development in ICR-CD1 female mice","volume":"12","author":"Deulofeu","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1089\/neu.2006.23.635","article-title":"Basso Mouse Scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains","volume":"23","author":"Basso","year":"2006","journal-title":"J. Neurotrauma"},{"key":"ref_82","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"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/0304-3959(88)90026-7","article-title":"A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia","volume":"32","author":"Hargreaves","year":"1988","journal-title":"Pain"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/S0014-2999(03)01274-3","article-title":"The mouse light\/dark box test","volume":"463","author":"Bourin","year":"2003","journal-title":"Eur. J. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/S0006-3223(02)01827-9","article-title":"Validation of a simple, ethologically relevant paradigm for assessing anxiety in mice","volume":"54","author":"Merali","year":"2003","journal-title":"Biol. Psychiatry"},{"key":"ref_86","first-page":"140","article-title":"Behavioral phenotyping of rodents","volume":"53","author":"Crawley","year":"2003","journal-title":"Comp. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_88","unstructured":"Franklin, K.B.J., and Paxinos, G. (2013). Paxinos and Franklin\u2019s the Mouse Brain in Stereotaxic Coordinates, Academic Press."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s00418-002-0411-5","article-title":"A quantitative immunohistochemical study of the endoneurium in the rat dorsal and ventral spinal roots","volume":"117","year":"2002","journal-title":"Histochem. Cell. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1761\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:07:10Z","timestamp":1760119630000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/2\/1761"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,16]]},"references-count":89,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["ijms24021761"],"URL":"https:\/\/doi.org\/10.3390\/ijms24021761","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,16]]}}}