{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T09:54:17Z","timestamp":1778925257245,"version":"3.51.4"},"reference-count":83,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T00:00:00Z","timestamp":1630972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministerio del Poder Popular para Ciencia y Tecnolog\u00eda, Mission Science Program, and ENI DACION-BV.","award":["2007000881"],"award-info":[{"award-number":["2007000881"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cancer pain may be the consequence of physical nerve compression by a growing tumor. We employed a murine model to study whether gabapentin was able to regulate tumor growth, in addition to controlling hyperalgesic symptoms. A fluorescent melanoma cell line (B16\u2013BL6\/Zs green) was inoculated into the proximity of the sciatic nerve in male C57BL\/6 mice. The tumor gradually compressed the nerve, causing hypersensitivity. Tumor growth was characterized via in vivo imaging techniques. Every other day, gabapentin (100 mg\/Kg) or saline was IP administered to each animal. In the therapeutic protocol, gabapentin was administered once the tumor had induced increased nociception. In the preventive protocol, gabapentin was administered before the appearance of the positive signs. Additionally, in vitro experiments were performed to determine gabapentin\u2019s effects on cell-line proliferation, the secretion of the chemokine CCL2, and calcium influx. In the therapeutically treated animals, baseline responses to noxious stimuli were recovered, and tumors were significantly reduced. Similarly, gabapentin reduced tumor growth during the preventive treatment, but a relapse was noticed when the administration stopped. Gabapentin also inhibited cell proliferation, the secretion of CCL2, and calcium influx. These results suggest that gabapentin might represent a multivalent strategy to control cancer-associated events in painful tumors.<\/jats:p>","DOI":"10.3390\/ijms22189671","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T10:24:25Z","timestamp":1631010265000},"page":"9671","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Concomitant Antihyperalgesic and Antitumor Effects of Gabapentin in a Murine Cancer Pain Model"],"prefix":"10.3390","volume":"22","author":[{"given":"Beatriz Elena","family":"Brito","sequence":"first","affiliation":[{"name":"Laboratorio de Patolog\u00eda Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC), Caracas 1020A, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5923-5942","authenticated-orcid":false,"given":"Mar\u00eda Alejandra","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Laboratorio de Patolog\u00eda Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC), Caracas 1020A, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yetsenia Mar\u00eda","family":"De Gouveia","sequence":"additional","affiliation":[{"name":"Laboratorio de Patolog\u00eda Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC), Caracas 1020A, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pura","family":"Bola\u00f1os","sequence":"additional","affiliation":[{"name":"Laboratorio de Fisiolog\u00eda Celular, Centro de Biof\u00edsica y Bioqu\u00edmica, Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC), Caracas 1020A, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sindy","family":"Devis","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofisiolog\u00eda, Centro de Biof\u00edsica y Bioqu\u00edmica, Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC), Caracas 1020A, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geraldinee","family":"Bernal","sequence":"additional","affiliation":[{"name":"Laboratorio de Patolog\u00eda Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC), Caracas 1020A, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00edctor Alejandro","family":"Tortorici-Brito","sequence":"additional","affiliation":[{"name":"Laboratorio de Patolog\u00eda Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC), Caracas 1020A, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leslie","family":"Baute","sequence":"additional","affiliation":[{"name":"Laboratorio de Patolog\u00eda Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC), Caracas 1020A, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0999-7666","authenticated-orcid":false,"given":"Gabriel","family":"D\u00edaz-Serrano","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofisiolog\u00eda, Centro de Biof\u00edsica y Bioqu\u00edmica, Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC), Caracas 1020A, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00edctor","family":"Tortorici","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurofisiolog\u00eda, Centro de Biof\u00edsica y Bioqu\u00edmica, Instituto Venezolano de Investigaciones Cient\u00edficas (IVIC), Caracas 1020A, Venezuela"},{"name":"Laboratorio de Neurociencia, Departamento de Ciencias del Comportamiento, Escuela de Psicolog\u00eda, Universidad Metropolitana (UNIMET), Caracas 1073, Venezuela"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1177\/0269216311400480","article-title":"How well is cancer pain treated?","volume":"25","author":"Foley","year":"2011","journal-title":"Palliat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sykes, N., Bennett, M., and Yuan, C.-S. (2008). Clinical Pain Management: Cancer Pain, Hodder Arnold. [2nd ed.].","DOI":"10.1201\/b13440"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/ejp.957","article-title":"Antinociceptive effect of systemically administered dipyrone (metamizol), magnesium chloride or both in a murine model of cancer","volume":"21","author":"Brito","year":"2017","journal-title":"Eur. J. Pain"},{"key":"ref_4","first-page":"1669","article-title":"Effects of morphine on cancer pain and tumor growth and metastasis","volume":"59","author":"Kuraishi","year":"2001","journal-title":"Nippon Rinsho."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0014-2999(02)01450-4","article-title":"Morphine analgesia suppresses tumor growth and metastasis in a mouse model of cancer pain produced by orthotopic tumor inoculation","volume":"441","author":"Sasamura","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0304-3959(02)00073-8","article-title":"A mouse model of neuropathic cancer pain","volume":"99","author":"Shimoyama","year":"2002","journal-title":"Pain"},{"key":"ref_7","unstructured":"World Health Organization (2020, July 13). Traitement de la Douleur Canc\u00e9reuse. Gen\u00e8ve: Organisation Mondiale de la Sant\u00e9. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/41712."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1177\/1049909111415511","article-title":"Unrelieved pain and suffering in patients with advanced cancer","volume":"29","author":"Mori","year":"2012","journal-title":"Am. J. Hosp. Palliat. Care"},{"key":"ref_9","first-page":"112","article-title":"Pharmacologic management of cancer pain","volume":"22","author":"Portenoy","year":"1995","journal-title":"Semin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10289","DOI":"10.1523\/JNEUROSCI.2851-07.2007","article-title":"Chemical interactions between fibrosarcoma cancer cells and sensory neurons contribute to cancer pain","volume":"27","author":"Khasabova","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1111\/j.1755-148X.2012.00978.x","article-title":"Functional expression of voltage-gated calcium channels in human melanoma","volume":"25","author":"Das","year":"2012","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1113\/jphysiol.1992.sp018938","article-title":"Potassium channels and regulation of proliferation of human melanoma cells","volume":"445","author":"Nilius","year":"1992","journal-title":"J. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s002329900066","article-title":"K+ Channels and the intracellular calcium signal in human melanoma cell proliferation","volume":"151","author":"Berweck","year":"1996","journal-title":"J. Membr. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nrm1155","article-title":"Calcium signaling: Dynamics, homeostasis and remodeling","volume":"4","author":"Berridge","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"849","DOI":"10.3390\/cancers7020813","article-title":"Voltage-gated ion channels in cancer cell proliferation","volume":"7","author":"Rao","year":"2015","journal-title":"Cancers"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5383","DOI":"10.1038\/onc.2014.467","article-title":"CACNA2D2 promotes tumorigenesis by stimulating cell proliferation and angiogenesis","volume":"34","author":"Warnier","year":"2015","journal-title":"Oncogene"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1254\/jphs.CR0050020","article-title":"Mechanisms of the antinociceptive action of gabapentin","volume":"100","author":"Cheng","year":"2006","journal-title":"J. Pharmacol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8748","DOI":"10.1523\/JNEUROSCI.2764-06.2006","article-title":"The calcium channel \u03b12\u03b4-2 subunit partitions with Ca\u22282.1 into lipid rafts in cerebellum: Implications for localization and function","volume":"26","author":"Davies","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.tips.2006.12.006","article-title":"Ca2+ channel alpha2delta ligands: Novel modulators of neurotransmission","volume":"28","author":"Dooley","year":"2007","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1016\/j.bja.2018.02.066","article-title":"Analgesic mechanisms of gabapentinoids and effects in experimental pain models: A narrative review","volume":"120","author":"Chincholkar","year":"2018","journal-title":"Br. J. Anesth."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1023\/B:JOBB.0000008028.41056.58","article-title":"Calcium channel \u03b12\u03b4 subunits: Differential expression, function, and drug binding","volume":"35","author":"Klugbauer","year":"2003","journal-title":"J. Bioenrg. Biomembr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S0028-3908(01)00181-2","article-title":"Gabapentin-mediated inhibition of voltage-activated Ca2+ channel currents in culture sensory neurons is dependent on culture conditions and channel subunit expression","volume":"42","author":"Martin","year":"2002","journal-title":"Neuropharmacology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1002\/syn.20115","article-title":"Gabapentin fails to alter P\/Q-type Ca2+ channel-mediated synaptic transmission in the hippocampus in vitro","volume":"55","author":"Brown","year":"2005","journal-title":"Synapse"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.coph.2005.11.003","article-title":"The mechanisms of action of gabapentin and pregabalin","volume":"6","author":"Sills","year":"2006","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.it.2005.08.001","article-title":"Chemokines, chemokine receptors and pain","volume":"26","author":"Abbadie","year":"2005","journal-title":"Trends Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/B978-0-12-385071-3.00003-4","article-title":"Targeting chemokine (C-C motif) ligand 2 (CCL2) as an example of translation of cancer molecular biology to clinic","volume":"95","author":"Zhang","year":"2010","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4428","DOI":"10.18632\/oncotarget.6599","article-title":"Overcoming melanoma resistance to vemurafenib by targeting CCL2-induced miR-34a, miR-100 and miR-125b","volume":"7","author":"Vergani","year":"2015","journal-title":"Oncotarget"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5865","DOI":"10.1523\/JNEUROSCI.5986-10.2011","article-title":"CCL2 Released from neuronal synaptic vesicles in the spinal cord is a major mediator of local inflammation and pain after peripheral nerve injury","volume":"31","author":"Pommier","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.cyto.2019.03.007","article-title":"Chemokines CCL2 and CCL7, but not CCL12, play a significant role in the development of pain-related behavior and opioid-induced analgesia","volume":"119","author":"Kwiatkowsky","year":"2019","journal-title":"Cytokine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1097\/PAS.0b013e3182a0a150","article-title":"Malignant melanotic schwannian tumor: A clinicopathologic, immunohistochemical, and gene expression profiling study of 40 cases, with a proposal for the reclassification of \u201cmelanotic schwannoma\u201d","volume":"38","author":"Dry","year":"2014","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_31","first-page":"587","article-title":"The selection and characterization of an invasive variant of the B16 melanoma","volume":"97","author":"Hart","year":"1979","journal-title":"Am. J. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1007\/s00210-012-0787-2","article-title":"CCL2 release at tumor level contributes to the hiperalgesia evoked by intratibial inoculation of NCTC 2472 but not B16-F10 cells in mice","volume":"385","author":"Pevida","year":"2012","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Umemura, M., Baljinnyam, E., Feske, S., De Lorenzo, M.S., Xie, L.-H., Feng, X., Oda, K., Makino, A., Fujita, T., and Yokoyama, U. (2014). Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089292"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1097\/00008390-200206000-00004","article-title":"Changes in the motility of B16F10 melanoma cells induced by alterations in resting calcium influx","volume":"12","author":"Cox","year":"2002","journal-title":"Melanoma Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1002\/ijc.22621","article-title":"Functional genomics of calcium channels in human melanoma cells","volume":"121","author":"Deli","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1038\/sj.bjc.6690680","article-title":"Ca2+-induced changes in energy metabolism and viability of melanoma cells","volume":"81","author":"Penso","year":"1999","journal-title":"Br. J. Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"706452","DOI":"10.1155\/2012\/706452","article-title":"Neurotropic melanoma: The management of localised disease","volume":"2012","author":"Croker","year":"2012","journal-title":"J. Skin Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3171\/jns.1974.41.2.0187","article-title":"Melanotic nerve sheath tumors","volume":"4","author":"Mandybur","year":"1974","journal-title":"J. Neurosurg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/S0306-4522(00)00110-X","article-title":"Murine models of inflammatory, neuropathic and cancer pain each generates a unique set of neurochemical changes in the spinal cord and sensory neurons","volume":"98","author":"Honore","year":"2000","journal-title":"Neuroscience"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9367","DOI":"10.1523\/JNEUROSCI.21-23-09367.2001","article-title":"Functional interactions between tumor and peripheral nerve: Changes in excitability and morphology of primary afferent fibers in a murine model of cancer pain","volume":"21","author":"Cain","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.brainres.2007.08.075","article-title":"Tumor-evoked hyperalgesia and sensitization of nociceptive dorsal horn neurons in a murine model of cancer pain","volume":"1180","author":"Khasabov","year":"2007","journal-title":"Brain Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Edwards, H.L., Mulvey, M.R., and Bennett, M.I. (2019). Cancer-related neuropathic pain. Cancers, 11.","DOI":"10.3390\/cancers11030373"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1248\/bpb.26.550","article-title":"Suppression by gabapentin of pain-related mechano-responses in mice given orthotopic tumor inoculation","volume":"26","author":"Kuraishi","year":"2003","journal-title":"Biol. Pharm. Bull."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ejphar.2009.01.014","article-title":"Oral pregabalin reverses cold allodynia in two distinct models of peripheral neuropathic pain","volume":"605","author":"Gustafsson","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1037\/1064-1297.14.1.42","article-title":"Adverse effects of gabapentin and lack of anti-allodynic efficacy of amitriptyline in the streptozotocin model of painful diabetic neuropathy","volume":"14","author":"Lindner","year":"2006","journal-title":"Exper. Clin. Psychopharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1358\/mf.2008.30.6.1232963","article-title":"Synergistic antiallodynic interaction between gabapentin or carbamazepine and either benfotiamine or cyanocobalamin in neuropathic rats","volume":"30","year":"2008","journal-title":"Methods Find Exp. Clin. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1527-3458.2004.tb00012.x","article-title":"The biology and pharmacology of calcium channel alpha2-delta proteins, Pfizer Satellite Symposium, 2003 Society for Neuroscience Meeting, Sheraton New Orleans Hotel, New Orleans, LA, EE.UU. 10 November 2003","volume":"10","author":"Taylor","year":"2004","journal-title":"CNS Drug Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5768","DOI":"10.1074\/jbc.271.10.5768","article-title":"The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel","volume":"271","author":"Gee","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1023\/A:1024078704020","article-title":"Gabapentin blocks L-type and P\/Q-type Ca2+ channels involved in oxide synthase activity in primary cultures of neurons from mouse cerebral cortex","volume":"20","author":"Oka","year":"2003","journal-title":"Pharm. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1042\/bj3420313","article-title":"Structural requirement of the calcium-channel subunit \u03b12\u03b4 for gabapentin binding","volume":"342","author":"Wang","year":"1999","journal-title":"Biochem. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/sj.bjp.0703380","article-title":"Inhibition of neuronal Ca(2+) influx by gabapentin and subsequent reduction of neurotransmitter release from rat neocortical slices","volume":"130","author":"Fink","year":"2000","journal-title":"Br. J. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/sj.bjp.0704227","article-title":"Block by gabapentin of the facilitation of glutamate release from rat trigeminal nucleus following activation of protein kinase C or adenylyl cyclase","volume":"134","author":"Maneuf","year":"2001","journal-title":"Br. J. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1111\/j.1460-9568.2004.03625.x","article-title":"Dual effects of gabapentin and pregabalin on glutamate release at rat entorhinal synapses in vitro","volume":"20","author":"Cunningham","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0304-3959(01)00316-5","article-title":"Gabapentin inhibits the substance P-facilitated K(+)-evoked release of [(3)H]glutamate from rat caudial trigeminal nucleus slices","volume":"93","author":"Maneuf","year":"2001","journal-title":"Pain"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/j.1460-9568.2004.03832.x","article-title":"Presynaptic NMDA autoreceptors facilitate axon excitability: A new molecular target for the anticonvulsant gabapentin","volume":"21","author":"Ruiz","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/S0028-3908(01)00172-1","article-title":"Inhibition of neuronal Ca2+ influx by gabapentin and pregabalin in the human neocortex","volume":"42","author":"Fink","year":"2002","journal-title":"Neuropharmacology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.eplepsyres.2006.09.008","article-title":"Pharmacology and mechanism of action of pregabalin: The calcium channel \u03b12-\u03b4 (alpha2-delta) subunit as a target for antiepileptic drug discovery","volume":"73","author":"Taylor","year":"2007","journal-title":"Epilepsy Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1016\/j.celrep.2018.02.021","article-title":"The \u03b12\u03b4-1-NMDA Receptor Complex Is Critically Involved in Neuropathic Pain Development and Gabapentin Therapeutic Actions","volume":"22","author":"Chen","year":"2018","journal-title":"Cell Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"7080","DOI":"10.1158\/1078-0432.CCR-11-0098","article-title":"Glutamatergic pathway targeting in melanoma: Single-agent and combinatorial therapies","volume":"17","author":"Lee","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4366","DOI":"10.1038\/onc.2012.471","article-title":"Metabotropic glutamate receptor 1 (Grm1) is an oncogene in epithelial cells","volume":"32","author":"Martino","year":"2013","journal-title":"Oncogene"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1158\/0008-5472.CAN-06-3665","article-title":"Metabotropic glutamate receptor 1 and glutamate signaling in human melanoma","volume":"67","author":"Namkoong","year":"2007","journal-title":"Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1111\/exd.12048","article-title":"Blocking glutamate-mediated signalling inhibits human melanoma growth and migration","volume":"21","author":"Song","year":"2012","journal-title":"Exp. Dermatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0165-5728(01)00340-X","article-title":"The involvement of glutamate in recall of the conditioned NK cell response","volume":"118","author":"Kuo","year":"2001","journal-title":"J. Neuroimmunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0169-328X(01)00188-7","article-title":"Dorsal root ganglion neurons show increased expression of the calcium channel alpha2delta-1 subunit following partial sciatic nerve injury","volume":"95","author":"Newton","year":"2001","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_65","first-page":"1026","article-title":"Gabapentin suppresses ectopic nerve discharges and reverses allodynia in neuropathic rats","volume":"288","author":"Pan","year":"1999","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"14092","DOI":"10.1073\/pnas.0503496102","article-title":"Excitatory monocyte chemoattractant protein-1 signaling is up-regulated in sensory neurons after chronic compression of the dorsal root ganglion","volume":"102","author":"White","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1152\/jn.00222.2006","article-title":"MCP-1 enhances excitability of nociceptive neurons in chronically compressed dorsal root ganglia","volume":"96","author":"Sun","year":"2006","journal-title":"J. Neurophysiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7947","DOI":"10.1073\/pnas.1331358100","article-title":"Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2","volume":"100","author":"Abbadie","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.1152\/jn.00183.2011","article-title":"CCL2 has similar excitatory effects to TNF-\u03b1 in a subgroup of inflamed C-fiber axons","volume":"106","author":"Richards","year":"2011","journal-title":"J. Neurophysiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1111\/j.1742-1241.2004.00284.x","article-title":"Cell proliferation and cell cycle control: A mini review","volume":"58","author":"Golias","year":"2004","journal-title":"Int. J. Clin. Pract."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1046\/j.1365-2184.2003.00266.x","article-title":"The cell cycle: A review of regulation, deregulation and therapeutic targets in cancer","volume":"36","author":"Vermeulen","year":"2003","journal-title":"Cell Prolif."},{"key":"ref_72","first-page":"587135","article-title":"Calcium cannel expression applicability as a targeted therapies in melanoma","volume":"2015","author":"Herreros","year":"2015","journal-title":"BioMed Res. Internat."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"13407","DOI":"10.18632\/oncotarget.24388","article-title":"Selenoprotein K deficiency inhibits melanoma by reducing calcium flux required for tumor growth and metastasis","volume":"9","author":"Marciel","year":"2018","journal-title":"Oncotarget"},{"key":"ref_74","unstructured":"Leary, S., Underwood, W., Anthony, R., Cartner, S., Grandin, T., Greenacre, C., Gwaltney-Brant, S., McCrakin, M.A., Meyer, R., and Miller, D. (2020). AVMA Guidelines for the Euthanasia of Animals: 2020 Edition, American Veterinary Medical Association."},{"key":"ref_75","unstructured":"National-Research-Council of the National Academies (2011). Guide for the Care and Use of Laboratory Animals, The National Academies Press. [8th ed.]."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.neuropharm.2018.10.006","article-title":"THC and gabapentin interactions in a mouse neuropathic pain model","volume":"144","author":"Atwal","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1159\/000370244","article-title":"Antinociceptive synergism of gabapentin and nortriptyline in mice with partial sciatic nerve ligation","volume":"95","author":"Miranda","year":"2015","journal-title":"Pharmacology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1017\/S0265021507001226","article-title":"Gabapentin action and interaction on the antinociceptive effect of morphine on visceral pain in mice","volume":"25","author":"Meymandi","year":"2008","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1046\/j.1528-1157.44.s10.5.x","article-title":"An in vitro study of new antiepileptic drugs and astrocytes","volume":"44","author":"Pavone","year":"2003","journal-title":"Epilepsia"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.jchromb.2007.03.039","article-title":"Validated HPLC method for the determination of gabapentin in human plasma using pre-column derivatization with 1-fluoro-2,4-dinitrobenzene and its application to a pharmacokinetic study","volume":"854","author":"Jalalizadeh","year":"2007","journal-title":"J. Chromatogr. B Analyt. Technol. Biomed Life Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.2147\/JPR.S162322","article-title":"Short-term incubation of gabapentin or pregabalin does not affect chemically induced injury in neuronal cell models in vitro","volume":"11","author":"Baldewig","year":"2018","journal-title":"J. Pain Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s12576-009-0039-5","article-title":"Factors affecting SOCE activation in mammalian skeletal muscle fibers","volume":"59","author":"DiPolo","year":"2009","journal-title":"J. Phisiol. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9671\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:57:59Z","timestamp":1760165879000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9671"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,7]]},"references-count":83,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms22189671"],"URL":"https:\/\/doi.org\/10.3390\/ijms22189671","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,7]]}}}