{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:21:35Z","timestamp":1792783295111,"version":"4.5.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":294,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universidad de Oviedo","id":[{"id":"https:\/\/ror.org\/006gksa02","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The neutralization of interleukin-16 (IL-16) or of its main target, CD4 receptors, as well as the reduction of its synthesis by inhibiting caspase-3 have been recently considered as possible strategies to inhibit pain. Here we study the involvement of peripheral mechanisms related to the IL-16\/CD4 axis in the nociceptive responses evoked after ligation of sciatic nerve in mice. Systemic administration of anti-IL-16 or anti-CD4 antibodies inhibited hyperalgesia and allodynia measured 2\u00a0days after ligation in male and female mice. In addition, both antibodies were also analgesic 9\u00a0days after nerve ligation, supporting the participation of IL-16 and CD4 in the establishment and maintenance of neuropathic pain. Following nerve injury,\n                    <jats:italic>Il16<\/jats:italic>\n                    expression remained unaltered in dorsal root ganglia (DRGs) and damaged nerves, whereas\n                    <jats:italic>Casp3<\/jats:italic>\n                    expression increased in DRGs and the enzymatic activity of caspase-3 was enhanced in damaged nerves. Immunofluorescence assays demonstrated a limited presence of IL-16 in DRG neurons, that remained unmodified after injury, and a clear up-regulation of this cytokine in injured nerves. Double immunofluorescence assays with \u03b2III-tubulin and S100\u03b2 antibodies demonstrated that IL-16 is expressed both in axons and Schwann cells after nerve ligation. The ability of IL-16 to evoke nociception by directly acting on nerves was confirmed by intra-sciatic administration. Immunofluorescence labelling of CD4 receptors was also present in injured nerves, being also up-regulated both in axons and Schwann cells. Finally, hyperalgesia and allodynia were prevented by the intra-sciatic administration of anti-IL-16 or anti-CD4 antibodies, thus supporting the relevance of the IL-16\/CD4 axis in neuropathic hypernociception.\n                  <\/jats:p>","DOI":"10.1007\/s12035-026-06280-2","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:32:13Z","timestamp":1792675933000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neural Expression of IL-16 Mediates Neuropathic Pain after Sciatic Injury in Mice"],"prefix":"10.1007","volume":"63","author":[{"given":"Alba","family":"Coro-Mart\u00edn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"\u00c1lvarez-Artime","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gonz\u00e1lez-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Gonz\u00e1lez-Amor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Corral-Fontecha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Baamonde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Men\u00e9ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"6280_CR1","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.bbi.2018.06.015","volume":"73","author":"HY Wu","year":"2018","unstructured":"Wu HY, Mao XF, Tang XQ, Ali U, Apryani E, Liu H, Li XY, Wang YX (2018) Spinal interleukin-10 produces antinociception in neuropathy through microglial \u03b2-endorphin expression, separated from antineuroinflammation. Brain Behav Immun 73:504\u2013519. https:\/\/doi.org\/10.1016\/j.bbi.2018.06.015","journal-title":"Brain Behav Immun"},{"key":"6280_CR2","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1007\/s40122-024-00603-8","volume":"13","author":"AD Kaye","year":"2024","unstructured":"Kaye AD, Perilloux DM, Hawkins AM, Wester GC, Ragaland AR, Hebert SV, Kim J, Heisler M, et al. (2024) Tumor necrosis factor and interleukin modulators for pathologic pain states: a narrative review. Pain Ther 13:481\u2013493. https:\/\/doi.org\/10.1007\/s40122-024-00603-8","journal-title":"Pain Ther"},{"key":"6280_CR3","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.sjpain.2017.08.002","volume":"17","author":"AL Hung","year":"2017","unstructured":"Hung AL, Lim M, Doshi TL (2017) Targeting cytokines for treatment of neuropathic pain. Scand J Pain 17:287\u2013293. https:\/\/doi.org\/10.1016\/j.sjpain.2017.08.002","journal-title":"Scand J Pain"},{"key":"6280_CR4","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1007\/s00109-024-02464-2","volume":"102","author":"J Ruivo","year":"2024","unstructured":"Ruivo J, Tavares I, Pozza DH (2024) Molecular targets in bone cancer pain: a systematic review of inflammatory cytokines. J Mol Med (Berl) 102:1063\u20131088. https:\/\/doi.org\/10.1007\/s00109-024-02464-2","journal-title":"J Mol Med (Berl)"},{"key":"6280_CR5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1524026","volume":"16","author":"TB Niewold","year":"2025","unstructured":"Niewold TB, Lehman JS, Gunnarsson I, Meves A, Oke V (2025) Role of interleukin-16 in human diseases: a novel potential therapeutic target. Front Immunol 16:1524026. https:\/\/doi.org\/10.3389\/fimmu.2025.1524026","journal-title":"Front Immunol"},{"key":"6280_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.113903","volume":"175","author":"A Aguirre","year":"2020","unstructured":"Aguirre A, Gonz\u00e1lez-Rodr\u00edguez S, Garc\u00eda-Dom\u00ednguez M, Lastra A, Guti\u00e9rrez-Fern\u00e1ndez A, Hidalgo A, Men\u00e9ndez L, Baamonde A (2020) Dual dose-related effects evoked by CCL4 on thermal nociception after gene delivery or exogenous administration in mice. Biochem Pharmacol 175:113903. https:\/\/doi.org\/10.1016\/j.bcp.2020.113903","journal-title":"Biochem Pharmacol"},{"key":"6280_CR7","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1007\/s11481-024-10145-7","volume":"19","author":"S Gonz\u00e1lez-Rodr\u00edguez","year":"2024","unstructured":"Gonz\u00e1lez-Rodr\u00edguez S, Sordo-Bahamonde C, \u00c1lvarez-Artime A, Baamonde A, Men\u00e9ndez L (2024) Hyperalgesic effect evoked by il-16 and its participation in inflammatory hypernociception in mice. J Neuroimmune Pharmacol 19:44. https:\/\/doi.org\/10.1007\/s11481-024-10145-7","journal-title":"J Neuroimmune Pharmacol"},{"key":"6280_CR8","doi-asserted-by":"publisher","first-page":"6485","DOI":"10.1007\/s00210-025-04810-8","volume":"399","author":"X Li","year":"2025","unstructured":"Li X, Wang R, Ma X, Yang J, Zhang S, Zhang Z, Jiang H, Liu J, et al. (2025) Glaucine suppresses IL-16\/CD4 to alleviate neuropathic pain via spinal p56lck-NMDA receptor signaling. Naunyn Schmiedebergs Arch Pharmacol 399:6485\u20136500. https:\/\/doi.org\/10.1007\/s00210-025-04810-8","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"6280_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2024.110115","volume":"259","author":"X Zhu","year":"2024","unstructured":"Zhu X, Li X, Liu S, Zhao YH, Liu XR, Liu XY, Yao R, Tian L, et al. (2024) Enhanced interleukin-16-CD4 signaling in CD3 T cell mediates neuropathic pain via activating astrocytes in female mice. Neuropharmacology 259:110115. https:\/\/doi.org\/10.1016\/j.neuropharm.2024.110115","journal-title":"Neuropharmacology"},{"key":"6280_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.111411","volume":"127","author":"X Zhu","year":"2024","unstructured":"Zhu X, Liu S, Tian L, Li X, Yao R, Zhao Y, Gao Z, Liu XR, et al. (2024) Spinal interleukin-16 mediates inflammatory pain via promoting glial activation. Int Immunopharmacol 127:111411. https:\/\/doi.org\/10.1016\/j.intimp.2023.111411","journal-title":"Int Immunopharmacol"},{"key":"6280_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.177861","volume":"1002","author":"L Men\u00e9ndez","year":"2025","unstructured":"Men\u00e9ndez L, \u00c1lvarez-Artime A, Gonz\u00e1lez-Rodr\u00edguez S, Fern\u00e1ndez-Garc\u00eda G, Gonz\u00e1lez-Amor M, Manteca \u00c1, Baamonde A (2025) Involvement of protein A and IL-16 in the hyperalgesia and allodynia evoked by Staphylococcus aureus in mice. Eur J Pharmacol 1002:177861. https:\/\/doi.org\/10.1016\/j.ejphar.2025.177861","journal-title":"Eur J Pharmacol"},{"key":"6280_CR12","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1172\/JCI36246","volume":"119","author":"D Labuz","year":"2009","unstructured":"Labuz D, Schmidt Y, Schreiter A, Rittner HL, Mousa SA, Machelska H (2009) Immune cell-derived opioids protect against neuropathic pain in mice. J Clin Invest 119:278\u2013286. https:\/\/doi.org\/10.1172\/JCI36246","journal-title":"J Clin Invest"},{"key":"6280_CR13","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1007\/s12035-018-1176-8","volume":"56","author":"M Garc\u00eda-Dom\u00ednguez","year":"2019","unstructured":"Garc\u00eda-Dom\u00ednguez M, Lastra A, Folgueras AR, Cernuda-Cernuda R, Fern\u00e1ndez-Garc\u00eda MT, Hidalgo A, Men\u00e9ndez L, Baamonde A (2019) The chemokine CCL4 (MIP-1\u03b2) evokes antinociceptive effects in mice: a role for CD4+ lymphocytes and met-enkephalin. Mol Neurobiol 56:1578\u20131595. https:\/\/doi.org\/10.1007\/s12035-018-1176-8","journal-title":"Mol Neurobiol"},{"key":"6280_CR14","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jim.2013.04.004","volume":"393","author":"L Loubaki","year":"2013","unstructured":"Loubaki L, Tremblay T, Bazin R (2013) In vivo depletion of leukocytes and platelets following injection of T cell-specific antibodies into mice. J Immunol Methods 393:38\u201344. https:\/\/doi.org\/10.1016\/j.jim.2013.04.004","journal-title":"J Immunol Methods"},{"key":"6280_CR15","doi-asserted-by":"publisher","first-page":"4503","DOI":"10.1128\/IAI.05799-11","volume":"79","author":"T Dejima","year":"2011","unstructured":"Dejima T, Shibata K, Yamada H, Hara H, Iwakura Y, Naito S, Yoshikai Y (2011) Protective role of naturally occurring interleukin-17A-producing \u03b3\u03b4 T cells in the lung at the early stage of systemic candidiasis in mice. Infect Immun 79:4503\u20134510. https:\/\/doi.org\/10.1128\/IAI.05799-11","journal-title":"Infect Immun"},{"key":"6280_CR16","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1038\/nprot.2014.073","volume":"9","author":"S Gonzalez","year":"2014","unstructured":"Gonzalez S, Fernando RN, Perrin-Tricaud C, Tricaud N (2014) In vivo introduction of transgenes into mouse sciatic nerve cells in situ using viral vectors. Nat Protoc 9:1160\u20131169. https:\/\/doi.org\/10.1038\/nprot.2014.073","journal-title":"Nat Protoc"},{"key":"6280_CR17","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/s0165-0270(01)00483-6","volume":"113","author":"L Men\u00e9ndez","year":"2002","unstructured":"Men\u00e9ndez L, Lastra A, Hidalgo A, Baamonde A (2002) Unilateral hot plate test: a simple and sensitive method for detecting central and peripheral hyperalgesia in mice. J Neurosci Methods 113:91\u201397. https:\/\/doi.org\/10.1016\/s0165-0270(01)00483-6","journal-title":"J Neurosci Methods"},{"key":"6280_CR18","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0165-0270(94)90144-9","volume":"53","author":"SR Chaplan","year":"1994","unstructured":"Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL (1994) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53:55\u201363. https:\/\/doi.org\/10.1016\/0165-0270(94)90144-9","journal-title":"J Neurosci Methods"},{"key":"6280_CR19","doi-asserted-by":"publisher","first-page":"3345","DOI":"10.1152\/jn.00973.2014","volume":"113","author":"K Ono","year":"2015","unstructured":"Ono K, Ye Y, Viet CT, Dang D, Schmidt BL (2015) TRPV1 expression level in isolectin B\u2084-positive neurons contributes to mouse strain difference in cutaneous thermal nociceptive sensitivity. J Neurophysiol 113:3345\u20133355. https:\/\/doi.org\/10.1152\/jn.00973.2014","journal-title":"J Neurophysiol"},{"key":"6280_CR20","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/j.jpain.2012.02.010","volume":"13","author":"M Kanngiesser","year":"2012","unstructured":"Kanngiesser M, H\u00e4ussler A, Myrczek T, K\u00fcsener N, Lim HY, Geisslinger G, Niederberger E, Tegeder I (2012) Inhibitor kappa B kinase beta dependent cytokine upregulation in nociceptive neurons contributes to nociceptive hypersensitivity after sciatic nerve injury. J Pain 13:485\u2013497. https:\/\/doi.org\/10.1016\/j.jpain.2012.02.010","journal-title":"J Pain"},{"key":"6280_CR21","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.985223","volume":"13","author":"Y Quan","year":"2022","unstructured":"Quan Y, Yin Z, Chen S, Lang J, Han L, Yi J, Zhang L, Yue Q, et al. (2022) The gut-lung axis: gut microbiota changes associated with pulmonary fibrosis in mouse models induced by bleomycin. Front Pharmacol 13:985223. https:\/\/doi.org\/10.3389\/fphar.2022.985223","journal-title":"Front Pharmacol"},{"key":"6280_CR22","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402\u2013408. https:\/\/doi.org\/10.1006\/meth.2001.1262","journal-title":"Methods"},{"key":"6280_CR23","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1002\/eji.200737485","volume":"38","author":"L Cao","year":"2008","unstructured":"Cao L, DeLeo JA (2008) CNS-infiltrating CD4+ T lymphocytes contribute to murine spinal nerve transection-induced neuropathic pain. Eur J Immunol 38:448\u2013458. https:\/\/doi.org\/10.1002\/eji.200737485","journal-title":"Eur J Immunol"},{"key":"6280_CR24","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/s0306-4522(00)00396-1","volume":"101","author":"NM Perkins","year":"2000","unstructured":"Perkins NM, Tracey DJ (2000) Hyperalgesia due to nerve injury: role of neutrophils. Neuroscience 101:745\u2013757. https:\/\/doi.org\/10.1016\/s0306-4522(00)00396-1","journal-title":"Neuroscience"},{"key":"6280_CR25","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1074\/jbc.273.2.1144","volume":"273","author":"Y Zhang","year":"1998","unstructured":"Zhang Y, Center DM, Wu DM, Cruikshank WW, Yuan J, Andrews DW, Kornfeld H (1998) Processing and activation of pro-interleukin-16 by caspase-3. J Biol Chem 273:1144\u20131149. https:\/\/doi.org\/10.1074\/jbc.273.2.1144","journal-title":"J Biol Chem"},{"key":"6280_CR26","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.brainres.2018.06.001","volume":"1696","author":"G Garc\u00eda","year":"2018","unstructured":"Garc\u00eda G, Mart\u00ednez-Rojas VA, Oviedo N, Murbarti\u00e1n J (2018) Blockade of anoctamin-1 in injured and uninjured nerves reduces neuropathic pain. Brain Res 1696:38\u201348. https:\/\/doi.org\/10.1016\/j.brainres.2018.06.001","journal-title":"Brain Res"},{"key":"6280_CR27","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1097\/WNR.0000000000001031","volume":"29","author":"R Wiberg","year":"2018","unstructured":"Wiberg R, Novikova LN, Kingham PJ (2018) Evaluation of apoptotic pathways in dorsal root ganglion neurons following peripheral nerve injury. NeuroReport 29:779\u2013785. https:\/\/doi.org\/10.1097\/WNR.0000000000001031","journal-title":"NeuroReport"},{"key":"6280_CR28","doi-asserted-by":"publisher","first-page":"4746","DOI":"10.3390\/ijms22094746","volume":"22","author":"SH Chen","year":"2021","unstructured":"Chen SH, Wu CC, Lin SC, Tseng WL, Huang TC, Yadav A, Lu FI, Liu YH, et al. (2021) Investigation of neuropathology after nerve release in chronic constriction injury of rat sciatic nerve. Int J Mol Sci 22:4746. https:\/\/doi.org\/10.3390\/ijms22094746","journal-title":"Int J Mol Sci"},{"key":"6280_CR29","doi-asserted-by":"publisher","first-page":"68","DOI":"10.5607\/en.2012.21.2.68","volume":"21","author":"H Vang","year":"2012","unstructured":"Vang H, Chung G, Kim HY, Park SB, Jung SJ, Kim JS, Oh SB (2012) Neurochemical properties of dental primary afferent neurons. Exp Neurol 21:68\u201374. https:\/\/doi.org\/10.5607\/en.2012.21.2.68","journal-title":"Exp Neurol"},{"issue":"14","key":"6280_CR30","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2031-23.2024","volume":"44","author":"P Gobrecht","year":"2024","unstructured":"Gobrecht P, Gebel J, Hilla A, Gisselmann G, Fischer D (2024) Targeting vasohibins to promote axon regeneration. J Neurosci 44(14):e2031232024. https:\/\/doi.org\/10.1523\/JNEUROSCI.2031-23.2024","journal-title":"J Neurosci"},{"key":"6280_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101791","volume":"5","author":"X Yao","year":"2024","unstructured":"Yao X, Kong L, Qiao Y, Brand D, Li J, Yan Z, Zheng SG, Qian Y, et al. (2024) Schwann cell-secreted frizzled-related protein 1 dictates neuroinflammation and peripheral nerve degeneration after neurotrauma. Cell Rep Med 5:101791. https:\/\/doi.org\/10.1016\/j.xcrm.2024.101791","journal-title":"Cell Rep Med"},{"key":"6280_CR32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1012397","volume":"20","author":"S Xu","year":"2024","unstructured":"Xu S, Li H, Ai Z, Guo R, Cheng H, Wang Y (2024) Exploring viral neuropathic pain: molecular mechanisms and therapeutic implications. PLoS Pathog 20:e1012397. https:\/\/doi.org\/10.1371\/journal.ppat.1012397","journal-title":"PLoS Pathog"},{"key":"6280_CR33","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/j.1750-3639.2001.tb00378.x","volume":"11","author":"S Jander","year":"2001","unstructured":"Jander S, Lausberg F, Stoll G (2001) Differential recruitment of CD8+ macrophages during Wallerian degeneration in the peripheral and central nervous system. Brain Pathol 11:27\u201338. https:\/\/doi.org\/10.1111\/j.1750-3639.2001.tb00378.x","journal-title":"Brain Pathol"},{"key":"6280_CR34","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1186\/s12905-023-02362-8","volume":"23","author":"OA Babah","year":"2023","unstructured":"Babah OA, Ojewunmi OO, Onwuamah CK, Udenze IC, Osuntoki AA, Afolabi BB (2023) Serum concentrations of IL-16 and its genetic polymorphism rs4778889 affect the susceptibility and severity of endometriosis in Nigerian women. BMC Womens Health 23:253. https:\/\/doi.org\/10.1186\/s12905-023-02362-8","journal-title":"BMC Womens Health"},{"key":"6280_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-43846-8","volume":"9","author":"SM Robinson","year":"2019","unstructured":"Robinson SM, Rasch S, Beer S, Valantiene I, Mickevicius A, Schlaipfer E, Mann J, Maisonneuve P, et al. (2019) Systemic inflammation contributes to impairment of quality of life in chronic pancreatitis. Sci Rep 9:7318. https:\/\/doi.org\/10.1038\/s41598-019-43846-8","journal-title":"Sci Rep"},{"key":"6280_CR36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1888076","volume":"17","author":"JW Kosid\u0142o","year":"2026","unstructured":"Kosid\u0142o JW, Dorf J, Kami\u0144ska J, Koper-Lenkiewicz OM, \u017baczek M, Saniuk P, Zimnoch K, Panasiuk A, et al. (2026) Unveiling the multidimensional cytokine landscape in acute pancreatitis. Front Immunol 17:1888076. https:\/\/doi.org\/10.3389\/fimmu.2026.1888076","journal-title":"Front Immunol"},{"key":"6280_CR37","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s12891-016-1375-2","volume":"18","author":"JA Singh","year":"2017","unstructured":"Singh JA, Noorbaloochi S, Knutson KL (2017) Cytokine and neuropeptide levels are associated with pain relief in patients with chronically painful total knee arthroplasty: a pilot study. BMC Musculoskelet Disord 18:17. https:\/\/doi.org\/10.1186\/s12891-016-1375-2","journal-title":"BMC Musculoskelet Disord"},{"key":"6280_CR38","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.bbi.2023.12.016","volume":"116","author":"L Brusaferri","year":"2024","unstructured":"Brusaferri L, Alshelh Z, Schnieders JH, Sandstr\u00f6m A, Mohammadian M, Morrissey EJ, Kim M, Chane CA, et al. (2024) Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset. Brain Behav Immun 116:259\u2013266. https:\/\/doi.org\/10.1016\/j.bbi.2023.12.016","journal-title":"Brain Behav Immun"},{"key":"6280_CR39","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2026.1796130","volume":"17","author":"H Liu","year":"2026","unstructured":"Liu H, Liu ZW, Zhang JT, Wang XL, Chen LH, Jin XH, Liu T, Ji FH (2026) Immune profiling in trigeminal neuralgia reveals altered cytokine and chemokine signatures in cerebrospinal fluid and serum. Front Pharmacol 17:1796130. https:\/\/doi.org\/10.3389\/fphar.2026.1796130","journal-title":"Front Pharmacol"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-026-06280-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-026-06280-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-026-06280-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T13:32:14Z","timestamp":1792675934000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-026-06280-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["6280"],"URL":"https:\/\/doi.org\/10.1007\/s12035-026-06280-2","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"24 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 October 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All the protocols were approved by the Comit\u00e9 \u00c9tico de Experimentaci\u00f3n Animal de la Universidad de Oviedo (Spain) (Approval number: PROAE 28\u20132021 and PROAE 28\u20132025) and performed according to the guidelines of European Communities Council Directive (2010\/63\/EU).","order":1,"name":"Ethics","label":"Ethics Approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"987"}}