{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:35:56Z","timestamp":1790886956298,"version":"4.1.0"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T00:00:00Z","timestamp":1695254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Neutrophil extracellular traps (NETs) promote neuroinflammation and, thus, central nervous system (CNS) disease progression. However, it remains unclear whether CNS-associated NETs affect pain outcomes. A fasting-mimicking diet (FMD) alleviates neurological disorders by attenuating neuroinflammation and promoting nerve regeneration. Hence, in this study, we explore the role of NETs in the CNS during acute pain and investigate the role of FMD in inhibiting NETs and relieving pain.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The inflammatory pain model was established by injecting complete Freund\u2019s adjuvant (CFA) into the hind paw of mice. The FMD diet regimen was performed during the perioperative period. PAD4 siRNA or CI-amidine (PAD4 inhibitor) was used to inhibit the formation of NETs. Monoamine oxidase-B (MAO-B) knockdown occurred by AAV-GFAP-shRNA or AAV-hSyn-shRNA or was inhibited by selegiline (an MAO-B inhibitor). The changes in NETs, neuroinflammation, and related signaling pathways were examined by western blot, immunofluorescence, ELISA, and flow cytometry.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>In the acute phase of inflammatory pain, NETs accumulate in the spinal cords of mice. This is associated with exacerbated neuroinflammation. Meanwhile, inhibition of NETs formation alleviates allodynia and neuroinflammation in CFA mice. FMD inhibits NETs production and alleviates inflammatory pain, which is enhanced by treatment with the NETs inhibitor CI-amidine, and reversed by treatment with the NETs inducer phorbol 12-myristate 13-acetate (PMA). Mechanistically, the neutrophil-recruiting pathway MAO-B\/5-hydroxyindoleacetic acid (5-HIAA) \/ G-protein-coupled receptor 35 (GPR35) and NETs-inducing pathway MAO-B\/ Reactive oxygen species (ROS) are significantly upregulated during the development of inflammatory pain. MAO-B is largely expressed in astrocytes and neurons in the spinal cords of CFA mice. However, knockdown or inhibition of MAO-B effectively attenuates CFA-induced inflammatory pain, NETs formation, and neuroinflammation in the spinal cord. Moreover, within rescue experiments, MAO-B inhibitors synergistically enhance FMD-induced pain relief, NETs inhibition, and neuroinflammation attenuation, whereas supplementation with MAO-B downstream molecules (i.e., 5-HIAA and PMA) abolished this effect.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Neutrophil-released NETs in the spinal cord contribute to pain development. FMD inhibits NETs formation and NETs-induced neuroinflammation by inhibiting the MAO-B\/5-HIAA\/GPR35 and MAO-B\/ROS pathways in astrocytes and neurons, thereby relieving pain progression.<\/jats:p>\n                \n              <\/jats:sec>","DOI":"10.1186\/s12964-023-01258-2","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T09:02:24Z","timestamp":1695286944000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Fasting-mimicking diet alleviates inflammatory pain by inhibiting neutrophil extracellular traps formation and neuroinflammation in the spinal cord"],"prefix":"10.1186","volume":"21","author":[{"given":"Ting","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwen","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhong","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,21]]},"reference":[{"issue":"4","key":"1258_CR1","doi-asserted-by":"crossref","first-page":"359.e1","DOI":"10.1016\/j.jpain.2016.11.004","volume":"18","author":"CR Chapman","year":"2017","unstructured":"Chapman CR, Vierck CJ. The transition of acute postoperative pain to chronic pain: an integrative overview of research on mechanisms. J Pain. 2017;18(4):359.e1-359.e38.","journal-title":"J Pain"},{"issue":"2","key":"1258_CR2","first-page":"e22243","volume":"14","author":"MA Montero","year":"2022","unstructured":"Montero MA, Hanna M, Perrot S, Varrassi G. Avoid postoperative pain to prevent its Chronification: a narrative review. Cureus. 2022;14(2):e22243.","journal-title":"Cureus"},{"issue":"3","key":"1258_CR3","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1097\/ALN.0000000000002238","volume":"129","author":"P Richebe","year":"2018","unstructured":"Richebe P, Capdevila X, Rivat C. Persistent postsurgical pain: pathophysiology and preventative pharmacologic considerations. Anesthesiology. 2018;129(3):590\u2013607.","journal-title":"Anesthesiology"},{"issue":"7","key":"1258_CR4","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/nrd4334","volume":"13","author":"RR Ji","year":"2014","unstructured":"Ji RR, Xu ZZ, Gao YJ. Emerging targets in neuroinflammation-driven chronic pain. Nat Rev Drug Discov. 2014;13(7):533\u201348.","journal-title":"Nat Rev Drug Discov"},{"key":"1258_CR5","doi-asserted-by":"crossref","first-page":"104580","DOI":"10.1016\/j.phrs.2019.104580","volume":"151","author":"A Kanashiro","year":"2020","unstructured":"Kanashiro A, Hiroki CH, Da FD, Birbrair A, Ferreira RG, Bassi GS, Fonseca MD, Kusuda R, Cebinelli G, Da SK, et al. The role of neutrophils in neuro-immune modulation. Pharmacol Res. 2020;151:104580.","journal-title":"Pharmacol Res"},{"issue":"2","key":"1258_CR6","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1007\/s12016-020-08804-7","volume":"61","author":"V Mutua","year":"2021","unstructured":"Mutua V, Gershwin LJ. A Review of Neutrophil Extracellular Traps (NETs) in Disease: Potential Anti-NETs Therapeutics. Clin Rev Allergy Immunol. 2021;61(2):194\u2013211.","journal-title":"Clin Rev Allergy Immunol"},{"issue":"11","key":"1258_CR7","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/j.autrev.2017.09.012","volume":"16","author":"KH Lee","year":"2017","unstructured":"Lee KH, Kronbichler A, Park DD, Park Y, Moon H, Kim H, Choi JH, Choi Y, Shim S, Lyu IS, et al. Neutrophil extracellular traps (NETs) in autoimmune diseases: a comprehensive review. Autoimmun Rev. 2017;16(11):1160\u201373.","journal-title":"Autoimmun Rev"},{"issue":"6","key":"1258_CR8","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/s41419-023-05898-7","volume":"14","author":"L Mi","year":"2023","unstructured":"Mi L, Min X, Shi M, Liu L, Zhang Y, Zhu Y, Li P, Chai Y, Chen F, Deng Q, et al. Neutrophil extracellular traps aggravate neuronal endoplasmic reticulum stress and apoptosis via TLR9 after traumatic brain injury. Cell Death Dis. 2023;14(6):374.","journal-title":"Cell Death Dis"},{"issue":"8","key":"1258_CR9","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/nm.3913","volume":"21","author":"E Zenaro","year":"2015","unstructured":"Zenaro E, Pietronigro E, Della BV, Piacentino G, Marongiu L, Budui S, Turano E, Rossi B, Angiari S, Dusi S, et al. Neutrophils promote Alzheimer\u2019s disease-like pathology and cognitive decline via LFA-1 integrin. Nat Med. 2015;21(8):880\u20136.","journal-title":"Nat Med"},{"issue":"1","key":"1258_CR10","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1182\/blood.2020008913","volume":"138","author":"R Wang","year":"2021","unstructured":"Wang R, Zhu Y, Liu Z, Chang L, Bai X, Kang L, Cao Y, Yang X, Yu H, Shi MJ, et al. Neutrophil extracellular traps promote tPA-induced brain hemorrhage via cGAS in mice with stroke. Blood. 2021;138(1):91\u2013103.","journal-title":"Blood"},{"issue":"5","key":"1258_CR11","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1097\/MOH.0000000000000665","volume":"28","author":"F Denorme","year":"2021","unstructured":"Denorme F, Rustad JL, Campbell RA. Brothers in arms: platelets and neutrophils in ischemic stroke. Curr Opin Hematol. 2021;28(5):301\u20137.","journal-title":"Curr Opin Hematol"},{"issue":"1","key":"1258_CR12","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1007\/s12035-021-02635-z","volume":"59","author":"C Li","year":"2022","unstructured":"Li C, Xing Y, Zhang Y, Hua Y, Hu J, Bai Y. Neutrophil Extracellular Traps Exacerbate Ischemic Brain Damage. Mol Neurobiol. 2022;59(1):643\u201356.","journal-title":"Mol Neurobiol"},{"issue":"1","key":"1258_CR13","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.cmet.2015.05.012","volume":"22","author":"S Brandhorst","year":"2015","unstructured":"Brandhorst S, Choi IY, Wei M, Cheng CW, Sedrakyan S, Navarrete G, Dubeau L, Yap LP, Park R, Vinciguerra M, et al. A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan. Cell Metab. 2015;22(1):86\u201399.","journal-title":"Cell Metab"},{"issue":"377","key":"1258_CR14","doi-asserted-by":"crossref","first-page":"eaai8700","DOI":"10.1126\/scitranslmed.aai8700","volume":"9","author":"M Wei","year":"2017","unstructured":"Wei M, Brandhorst S, Shelehchi M, Mirzaei H, Cheng CW, Budniak J, Groshen S, Mack WJ, Guen E, Di Biase S, et al. Fasting-mimicking diet and markers\/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med. 2017;9(377):eaai8700.","journal-title":"Sci Transl Med"},{"issue":"13","key":"1258_CR15","doi-asserted-by":"crossref","first-page":"111417","DOI":"10.1016\/j.celrep.2022.111417","volume":"40","author":"P Rangan","year":"2022","unstructured":"Rangan P, Lobo F, Parrella E, Rochette N, Morselli M, Stephen TL, Cremonini AL, Tagliafico L, Persia A, Caffa I, et al. Fasting-mimicking diet cycles reduce neuroinflammation to attenuate cognitive decline in Alzheimer\u2019s models. Cell Rep. 2022;40(13):111417.","journal-title":"Cell Rep"},{"issue":"1","key":"1258_CR16","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1038\/s41467-020-15795-8","volume":"11","author":"ML Weng","year":"2020","unstructured":"Weng ML, Chen WK, Chen XY, Lu H, Sun ZR, Yu Q, Sun PF, Xu YJ, Zhu MM, Jiang N, et al. Fasting inhibits aerobic glycolysis and proliferation in colorectal cancer via the Fdft1-mediated AKT\/mTOR\/HIF1alpha pathway suppression. Nat Commun. 2020;11(1):1869.","journal-title":"Nat Commun"},{"issue":"7919","key":"1258_CR17","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/s41586-022-04884-x","volume":"607","author":"E Serger","year":"2022","unstructured":"Serger E, Luengo-Gutierrez L, Chadwick JS, Kong G, Zhou L, Crawford G, Danzi MC, Myridakis A, Brandis A, Bello AT, et al. The gut metabolite indole-3 propionate promotes nerve regeneration and repair. Nature. 2022;607(7919):585\u201392.","journal-title":"Nature"},{"issue":"2","key":"1258_CR18","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1007\/s11916-010-0104-z","volume":"14","author":"A Michalsen","year":"2010","unstructured":"Michalsen A. Prolonged fasting as a method of mood enhancement in chronic pain syndromes: a review of clinical evidence and mechanisms. Curr Pain Headache Rep. 2010;14(2):80\u20137.","journal-title":"Curr Pain Headache Rep"},{"issue":"1","key":"1258_CR19","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1038\/s41467-020-16243-3","volume":"11","author":"M Di Tano","year":"2020","unstructured":"Di Tano M, Raucci F, Vernieri C, Caffa I, Buono R, Fanti M, Brandhorst S, Curigliano G, Nencioni A, de Braud F, Longo VD. Synergistic effect of fasting-mimicking diet and vitamin C against KRAS mutated cancers. Nat Commun. 2020;11(1):2332.","journal-title":"Nat Commun"},{"issue":"5","key":"1258_CR20","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.cell.2017.01.040","volume":"168","author":"CW Cheng","year":"2017","unstructured":"Cheng CW, Villani V, Buono R, Wei M, Kumar S, Yilmaz OH, Cohen P, Sneddon JB, Perin L, Longo VD. Fasting-Mimicking Diet Promotes Ngn3-Driven beta-Cell Regeneration to Reverse Diabetes. Cell. 2017;168(5):775-788.e12.","journal-title":"Cell"},{"issue":"1","key":"1258_CR21","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1186\/s12974-020-01891-5","volume":"17","author":"T Li","year":"2020","unstructured":"Li T, Liu T, Chen X, Li L, Feng M, Zhang Y, Wan L, Zhang C, Yao W. Microglia induce the transformation of A1\/A2 reactive astrocytes via the CXCR7\/PI3K\/Akt pathway in chronic post-surgical pain. J Neuroinflammation. 2020;17(1):211.","journal-title":"J Neuroinflammation"},{"issue":"3","key":"1258_CR22","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1002\/glia.23552","volume":"67","author":"Q Li","year":"2019","unstructured":"Li Q, Liu S, Li L, Ji X, Wang M, Zhou J. Spinal IL-36gamma\/IL-36R participates in the maintenance of chronic inflammatory pain through astroglial JNK pathway. Glia. 2019;67(3):438\u201351.","journal-title":"Glia"},{"key":"1258_CR23","doi-asserted-by":"crossref","first-page":"227","DOI":"10.3389\/fimmu.2016.00227","volume":"7","author":"Y Kusunoki","year":"2016","unstructured":"Kusunoki Y, Nakazawa D, Shida H, Hattanda F, Miyoshi A, Masuda S, Nishio S, Tomaru U, Atsumi T, Ishizu A. Peptidylarginine deiminase inhibitor suppresses neutrophil extracellular trap formation and MPO-ANCA Production. Front Immunol. 2016;7:227.","journal-title":"Front Immunol"},{"issue":"1","key":"1258_CR24","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1038\/s41467-020-16191-y","volume":"11","author":"L Kang","year":"2020","unstructured":"Kang L, Yu H, Yang X, Zhu Y, Bai X, Wang R, Cao Y, Xu H, Luo H, Lu L, et al. Neutrophil extracellular traps released by neutrophils impair revascularization and vascular remodeling after stroke. Nat Commun. 2020;11(1):2488.","journal-title":"Nat Commun"},{"issue":"5","key":"1258_CR25","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.pharep.2018.05.004","volume":"70","author":"S Ostadhadi","year":"2018","unstructured":"Ostadhadi S, Shakiba S, Norouzi-Javidan A, Nikoui V, Zolfaghari S, Chamanara M, Dehpour AR. The role of nitric oxide-cGMP pathway in selegiline antidepressant-like effect in the mice forced swim test. Pharmacol Rep. 2018;70(5):1015\u201322.","journal-title":"Pharmacol Rep"},{"issue":"3","key":"1258_CR26","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1007\/s13311-021-01077-8","volume":"18","author":"P Jin","year":"2021","unstructured":"Jin P, Deng S, Sherchan P, Cui Y, Huang L, Li G, Lian L, Xie S, Lenahan C, Travis ZD, et al. Neurokinin Receptor 1 (NK1R) Antagonist Aprepitant Enhances Hematoma Clearance by Regulating Microglial Polarization via PKC\/p38MAPK\/NFkappaB Pathway After Experimental Intracerebral Hemorrhage in Mice. Neurotherapeutics. 2021;18(3):1922\u201338.","journal-title":"Neurotherapeutics"},{"issue":"5","key":"1258_CR27","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/j.cell.2022.01.010","volume":"185","author":"M De Giovanni","year":"2022","unstructured":"De Giovanni M, Tam H, Valet C, Xu Y, Looney MR, Cyster JG. GPR35 promotes neutrophil recruitment in response to serotonin metabolite 5-HIAA. Cell. 2022;185(5):815-830.e19.","journal-title":"Cell"},{"issue":"22","key":"1258_CR28","doi-asserted-by":"crossref","first-page":"4951","DOI":"10.1113\/jphysiol.2014.278754","volume":"592","author":"BE Yoon","year":"2014","unstructured":"Yoon BE, Woo J, Chun YE, Chun H, Jo S, Bae JY, An H, Min JO, Oh SJ, Han KS, et al. Glial GABA, synthesized by monoamine oxidase B, mediates tonic inhibition. J Physiol. 2014;592(22):4951\u201368.","journal-title":"J Physiol"},{"key":"1258_CR29","doi-asserted-by":"crossref","first-page":"630869","DOI":"10.3389\/fmolb.2021.630869","volume":"8","author":"GC Kretzschmar","year":"2021","unstructured":"Kretzschmar GC, Bumiller-Bini V, Gasparetto FM, Zonta YR, Yu K, de Souza R, Dias-Melicio LA, Boldt A. Neutrophil extracellular traps: a perspective of Neuroinflammation and complement activation in Alzheimer\u2019s disease. Front Mol Biosci. 2021;8:630869.","journal-title":"Front Mol Biosci"},{"issue":"26","key":"1258_CR30","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1056\/NEJMra1905136","volume":"381","author":"R de Cabo","year":"2019","unstructured":"de Cabo R, Mattson MP. Effects of Intermittent Fasting on Health, Aging, and Disease. N Engl J Med. 2019;381(26):2541\u201351.","journal-title":"N Engl J Med"},{"issue":"3","key":"1258_CR31","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nm.4294","volume":"23","author":"SK Jorch","year":"2017","unstructured":"Jorch SK, Kubes P. An emerging role for neutrophil extracellular traps in noninfectious disease. Nat Med. 2017;23(3):279\u201387.","journal-title":"Nat Med"},{"key":"1258_CR32","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.freeradbiomed.2021.01.020","volume":"165","author":"J Heger","year":"2021","unstructured":"Heger J, Hirschhauser C, Bornbaum J, Sydykov A, Dempfle A, Schneider A, Braun T, Schluter KD, Schulz R. Cardiomyocytes-specific deletion of monoamine oxidase B reduces irreversible myocardial ischemia\/reperfusion injury. Free Radic Biol Med. 2021;165:14\u201323.","journal-title":"Free Radic Biol Med"},{"issue":"10289","key":"1258_CR33","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1016\/S0140-6736(21)00393-7","volume":"397","author":"SP Cohen","year":"2021","unstructured":"Cohen SP, Vase L, Hooten WM. Chronic pain: an update on burden, best practices, and new advances. Lancet. 2021;397(10289):2082\u201397.","journal-title":"Lancet"},{"issue":"1","key":"1258_CR34","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.brainres.2006.08.085","volume":"1120","author":"TA Brooks","year":"2006","unstructured":"Brooks TA, Ocheltree SM, Seelbach MJ, Charles RA, Nametz N, Egleton RD, Davis TP. Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain. Brain Res. 2006;1120(1):172\u201382.","journal-title":"Brain Res"},{"issue":"30","key":"1258_CR35","doi-asserted-by":"crossref","first-page":"10819","DOI":"10.1523\/JNEUROSCI.1642-11.2011","volume":"31","author":"S Echeverry","year":"2011","unstructured":"Echeverry S, Shi XQ, Rivest S, Zhang J. Peripheral nerve injury alters blood-spinal cord barrier functional and molecular integrity through a selective inflammatory pathway. J Neurosci. 2011;31(30):10819\u201328.","journal-title":"J Neurosci"},{"issue":"1\u20132","key":"1258_CR36","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.pain.2007.10.024","volume":"134","author":"K Mitchell","year":"2008","unstructured":"Mitchell K, Yang HY, Tessier PA, Muhly WT, Swaim WD, Szalayova I, Keller JM, Mezey E, Iadarola MJ. Localization of S100A8 and S100A9 expressing neutrophils to spinal cord during peripheral tissue inflammation. Pain. 2008;134(1\u20132):216\u201331.","journal-title":"Pain"},{"issue":"12","key":"1258_CR37","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.3390\/cells8121477","volume":"8","author":"A Manda-Handzlik","year":"2019","unstructured":"Manda-Handzlik A, Demkow U. The brain entangled: the contribution of neutrophil extracellular traps to the diseases of the central nervous system. Cells-Basel. 2019;8(12):1477.","journal-title":"Cells-Basel"},{"issue":"1","key":"1258_CR38","doi-asserted-by":"crossref","first-page":"381","DOI":"10.4049\/jimmunol.1200409","volume":"189","author":"C Allen","year":"2012","unstructured":"Allen C, Thornton P, Denes A, Mccoll BW, Pierozynski A, Monestier M, Pinteaux E, Rothwell NJ, Allan SM. Neutrophil cerebrovascular transmigration triggers rapid neurotoxicity through release of proteases associated with decondensed DNA. J Immunol. 2012;189(1):381\u201392.","journal-title":"J Immunol"},{"issue":"6312","key":"1258_CR39","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1126\/science.aaf8924","volume":"354","author":"RR Ji","year":"2016","unstructured":"Ji RR, Chamessian A, Zhang YQ. Pain regulation by non-neuronal cells and inflammation. Science. 2016;354(6312):572\u20137.","journal-title":"Science"},{"issue":"4","key":"1258_CR40","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1111\/jnc.12744","volume":"130","author":"S Lange","year":"2014","unstructured":"Lange S, Rocha-Ferreira E, Thei L, Mawjee P, Bennett K, Thompson PR, Subramanian V, Nicholas AP, Peebles D, Hristova M, Raivich G. Peptidylarginine deiminases: novel drug targets for prevention of neuronal damage following hypoxic ischemic insult (HI) in neonates. J Neurochem. 2014;130(4):555\u201362.","journal-title":"J Neurochem"},{"issue":"9","key":"1258_CR41","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1016\/j.bmc.2017.03.006","volume":"25","author":"A Sarswat","year":"2017","unstructured":"Sarswat A, Wasilewski E, Chakka SK, Bello AM, Caprariello AV, Muthuramu CM, Stys PK, Dunn SE, Kotra LP. Inhibitors of protein arginine deiminases and their efficacy in animal models of multiple sclerosis. Bioorg Med Chem. 2017;25(9):2643\u201356.","journal-title":"Bioorg Med Chem"},{"issue":"1","key":"1258_CR42","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s12974-022-02474-2","volume":"19","author":"S Dai","year":"2022","unstructured":"Dai S, Wei J, Zhang H, Luo P, Yang Y, Jiang X, Fei Z, Liang W, Jiang J, Li X. Intermittent fasting reduces neuroinflammation in intracerebral hemorrhage through the Sirt3\/Nrf2\/HO-1 pathway. J Neuroinflammation. 2022;19(1):122.","journal-title":"J Neuroinflammation"},{"issue":"5","key":"1258_CR43","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.3945\/ajcn.116.136390","volume":"104","author":"N Veronese","year":"2016","unstructured":"Veronese N, Stubbs B, Noale M, Solmi M, Luchini C, Maggi S. Adherence to the Mediterranean diet is associated with better quality of life: data from the Osteoarthritis Initiative. Am J Clin Nutr. 2016;104(5):1403\u20139.","journal-title":"Am J Clin Nutr"},{"issue":"11","key":"1258_CR44","doi-asserted-by":"crossref","first-page":"6698","DOI":"10.3390\/ijerph19116698","volume":"19","author":"M Cuevas-Cervera","year":"2022","unstructured":"Cuevas-Cervera M, Perez-Montilla JJ, Gonzalez-Munoz A, Garcia-Rios MC, Navarro-Ledesma S. The effectiveness of intermittent fasting, time restricted feeding, caloric restriction, a ketogenic diet and the mediterranean diet as part of the treatment plan to improve health and chronic musculoskeletal pain: a systematic review. Int J Environ Res Public Health. 2022;19(11):6698.","journal-title":"Int J Environ Res Public Health"},{"issue":"1","key":"1258_CR45","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1158\/2159-8290.CD-21-0030","volume":"12","author":"C Vernieri","year":"2022","unstructured":"Vernieri C, Fuca G, Ligorio F, Huber V, Vingiani A, Iannelli F, Raimondi A, Rinchai D, Frige G, Belfiore A, et al. Fasting-mimicking diet is safe and reshapes metabolism and antitumor immunity in patients with cancer. Cancer Discov. 2022;12(1):90\u2013107.","journal-title":"Cancer Discov"},{"issue":"3","key":"1258_CR46","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.pain.2005.01.010","volume":"114","author":"WA Hargraves","year":"2005","unstructured":"Hargraves WA, Hentall ID. Analgesic effects of dietary caloric restriction in adult mice. Pain. 2005;114(3):455\u201361.","journal-title":"Pain"},{"issue":"1","key":"1258_CR47","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1096\/fj.201801033R","volume":"33","author":"S Boccella","year":"2019","unstructured":"Boccella S, Guida F, De Logu F, De Gregorio D, Mazzitelli M, Belardo C, Iannotta M, Serra N, Nassini R, de Novellis V, et al. Ketones and pain: unexplored role of hydroxyl carboxylic acid receptor type 2 in the pathophysiology of neuropathic pain. Faseb J. 2019;33(1):1062\u201373.","journal-title":"Faseb J"},{"issue":"4","key":"1258_CR48","doi-asserted-by":"crossref","first-page":"763","DOI":"10.4103\/1673-5374.354514","volume":"18","author":"K Taing","year":"2023","unstructured":"Taing K, Chen L, Weng HR. Emerging roles of GPR109A in regulation of neuroinflammation in neurological diseases and pain. Neural Regen Res. 2023;18(4):763\u20138.","journal-title":"Neural Regen Res"},{"issue":"4","key":"1258_CR49","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/glia.24130","volume":"70","author":"V Viatchenko-Karpinski","year":"2022","unstructured":"Viatchenko-Karpinski V, Kong L, Weng HR. Activation of microglial GPR109A alleviates thermal hyperalgesia in female lupus mice by suppressing IL-18 and glutamatergic synaptic activity. Glia. 2022;70(4):634\u201349.","journal-title":"Glia"},{"key":"1258_CR50","doi-asserted-by":"crossref","first-page":"109456","DOI":"10.1016\/j.neuropharm.2023.109456","volume":"228","author":"M Perrone","year":"2023","unstructured":"Perrone M, Pagano M, Belardo C, Ricciardi F, Ricciardi F, Fusco A, Trotta MC, Infantino R, Gargano F, Parente A, et al. Potential role of the hydroxyl carboxylic acid receptor type 2 (HCAR2) in microglia pathophysiology: A possible cross-talk with C-X-C chemokine receptor 1 (CXCR1). Neuropharmacology. 2023;228:109456.","journal-title":"Neuropharmacology"},{"issue":"9","key":"1258_CR51","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1007\/s00210-022-02247-x","volume":"395","author":"AG de Souza","year":"2022","unstructured":"de Souza AG, Lopes IS, Filho A, Cavalcante T, Oliveira J, de Carvalho M, de Lima KA, Juca PM, Mendonca SS, Mottin M, et al. Neuroprotective effects of dimethyl fumarate against depression-like behaviors via astrocytes and microglia modulation in mice: possible involvement of the HCAR2\/Nrf2 signaling pathway. Naunyn Schmiedebergs Arch Pharmacol. 2022;395(9):1029\u201345.","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"issue":"637","key":"1258_CR52","doi-asserted-by":"crossref","first-page":"eabl7634","DOI":"10.1126\/scitranslmed.abl7634","volume":"14","author":"M Moutinho","year":"2022","unstructured":"Moutinho M, Puntambekar SS, Tsai AP, Coronel I, Lin PB, Casali BT, Martinez P, Oblak AL, Lasagna-Reeves CA, Lamb BT, Landreth GE. The niacin receptor HCAR2 modulates microglial response and limits disease progression in a mouse model of Alzheimer\u2019s disease. Sci Transl Med. 2022;14(637):eabl7634.","journal-title":"Sci Transl Med."},{"issue":"5","key":"1258_CR53","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/s00401-020-02129-7","volume":"139","author":"KS Rawji","year":"2020","unstructured":"Rawji KS, Young A, Ghosh T, Michaels NJ, Mirzaei R, Kappen J, Kolehmainen KL, Alaeiilkhchi N, Lozinski B, Mishra MK, et al. Niacin-mediated rejuvenation of macrophage\/microglia enhances remyelination of the aging central nervous system. Acta Neuropathol. 2020;139(5):893\u2013909.","journal-title":"Acta Neuropathol"},{"key":"1258_CR54","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.lfs.2018.09.028","volume":"212","author":"F Nourbakhsh","year":"2018","unstructured":"Nourbakhsh F, Atabaki R, Roohbakhsh A. The role of orphan G protein-coupled receptors in the modulation of pain: a review. Life Sci. 2018;212:59\u201369.","journal-title":"Life Sci"},{"issue":"7\u20138","key":"1258_CR55","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1016\/j.neuropharm.2010.11.014","volume":"60","author":"C Cosi","year":"2011","unstructured":"Cosi C, Mannaioni G, Cozzi A, Carla V, Sili M, Cavone L, Maratea D, Moroni F. G-protein coupled receptor 35 (GPR35) activation and inflammatory pain: Studies on the antinociceptive effects of kynurenic acid and zaprinast. Neuropharmacology. 2011;60(7\u20138):1227\u201331.","journal-title":"Neuropharmacology"},{"issue":"2","key":"1258_CR56","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/nm.4027","volume":"22","author":"C Lood","year":"2016","unstructured":"Lood C, Blanco LP, Purmalek MM, Carmona-Rivera C, De Ravin SS, Smith CK, Malech HL, Ledbetter JA, Elkon KB, Kaplan MJ. Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease. Nat Med. 2016;22(2):146\u201353.","journal-title":"Nat Med"},{"issue":"3","key":"1258_CR57","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.pharmthera.2012.11.001","volume":"137","author":"W Kallenborn-Gerhardt","year":"2013","unstructured":"Kallenborn-Gerhardt W, Schroder K, Geisslinger G, Schmidtko A. NOXious signaling in pain processing. Pharmacol Ther. 2013;137(3):309\u201317.","journal-title":"Pharmacol Ther"},{"key":"1258_CR58","doi-asserted-by":"crossref","first-page":"101256","DOI":"10.1016\/j.arr.2021.101256","volume":"66","author":"Y Santin","year":"2021","unstructured":"Santin Y, Resta J, Parini A, Mialet-Perez J. Monoamine oxidases in age-associated diseases: New perspectives for old enzymes. Ageing Res Rev. 2021;66:101256.","journal-title":"Ageing Res Rev"},{"issue":"1","key":"1258_CR59","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/BF03165965","volume":"65","author":"Z Iffiu-Soltesz","year":"2009","unstructured":"Iffiu-Soltesz Z, Prevot D, Carpene C. Influence of prolonged fasting on monoamine oxidase and semicarbazide-sensitive amine oxidase activities in rat white adipose tissue. J Physiol Biochem. 2009;65(1):11\u201323.","journal-title":"J Physiol Biochem"},{"issue":"619","key":"1258_CR60","doi-asserted-by":"crossref","first-page":"eabj7152","DOI":"10.1126\/scitranslmed.abj7152","volume":"13","author":"A Kavelaars","year":"2021","unstructured":"Kavelaars A, Heijnen CJ. Immune regulation of pain: Friend and foe. Sci Transl Med. 2021;13(619):eabj7152.","journal-title":"Sci Transl Med."},{"key":"1258_CR61","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.conb.2019.11.006","volume":"62","author":"O Chen","year":"2020","unstructured":"Chen O, Donnelly CR, Ji RR. Regulation of pain by neuro-immune interactions between macrophages and nociceptor sensory neurons. Curr Opin Neurobiol. 2020;62:17\u201325.","journal-title":"Curr Opin Neurobiol"},{"issue":"2","key":"1258_CR62","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.immuni.2021.01.013","volume":"54","author":"RT Han","year":"2021","unstructured":"Han RT, Kim RD, Molofsky AV, Liddelow SA. Astrocyte-immune cell interactions in physiology and pathology. Immunity. 2021;54(2):211\u201324.","journal-title":"Immunity"},{"issue":"4","key":"1258_CR63","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.neuron.2020.08.012","volume":"108","author":"M Linnerbauer","year":"2020","unstructured":"Linnerbauer M, Wheeler MA, Quintana FJ. Astrocyte Crosstalk in CNS Inflammation. Neuron. 2020;108(4):608\u201322.","journal-title":"Neuron"},{"issue":"1","key":"1258_CR64","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3390\/ijms19010281","volume":"19","author":"V Coraggio","year":"2018","unstructured":"Coraggio V, Guida F, Boccella S, Scafuro M, Paino S, Romano D, Maione S, Luongo L. Neuroimmune-driven neuropathic pain establishment: a focus on gender differences. Int J Mol Sci. 2018;19(1):281.","journal-title":"Int J Mol Sci"},{"issue":"8","key":"1258_CR65","doi-asserted-by":"crossref","first-page":"2186","DOI":"10.1097\/j.pain.0000000000002215","volume":"162","author":"AM Gregus","year":"2021","unstructured":"Gregus AM, Levine IS, Eddinger KA, Yaksh TL, Buczynski MW. Sex differences in neuroimmune and glial mechanisms of pain. Pain. 2021;162(8):2186\u2013200.","journal-title":"Pain"},{"issue":"8","key":"1258_CR66","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1038\/nn.4053","volume":"18","author":"RE Sorge","year":"2015","unstructured":"Sorge RE, Mapplebeck JC, Rosen S, Beggs S, Taves S, Alexander JK, Martin LJ, Austin JS, Sotocinal SG, Chen D, et al. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci. 2015;18(8):1081\u20133.","journal-title":"Nat Neurosci"},{"issue":"7","key":"1258_CR67","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/s41583-020-0310-6","volume":"21","author":"JS Mogil","year":"2020","unstructured":"Mogil JS. Qualitative sex differences in pain processing: emerging evidence of a biased literature. Nat Rev Neurosci. 2020;21(7):353\u201365.","journal-title":"Nat Rev Neurosci"},{"issue":"6","key":"1258_CR68","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1523\/JNEUROSCI.21-06-01809.2001","volume":"21","author":"E Vegeto","year":"2001","unstructured":"Vegeto E, Bonincontro C, Pollio G, Sala A, Viappiani S, Nardi F, Brusadelli A, Viviani B, Ciana P, Maggi A. Estrogen prevents the lipopolysaccharide-induced inflammatory response in microglia. J Neurosci. 2001;21(6):1809\u201318.","journal-title":"J Neurosci"},{"issue":"24","key":"1258_CR69","doi-asserted-by":"crossref","first-page":"9505","DOI":"10.1073\/pnas.1118458109","volume":"109","author":"MA Zhang","year":"2012","unstructured":"Zhang MA, Rego D, Moshkova M, Kebir H, Chruscinski A, Nguyen H, Akkermann R, Stanczyk FZ, Prat A, Steinman L, Dunn SE. Peroxisome proliferator-activated receptor (PPAR)alpha and -gamma regulate IFNgamma and IL-17A production by human T cells in a sex-specific way. Proc Natl Acad Sci U S A. 2012;109(24):9505\u201310.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1258_CR70","first-page":"003","volume":"Suppl 3","author":"K Draleau","year":"2014","unstructured":"Draleau K, Maddula S, Slaiby A, Nutile-Mcmenemy N, De Leo J, Cao L. Phenotypic identification of spinal cord-infiltrating CD4(+) T lymphocytes in a murine model of neuropathic pain. J Pain Relief. 2014;Suppl 3:003.","journal-title":"J Pain Relief"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-023-01258-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12964-023-01258-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-023-01258-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T06:22:51Z","timestamp":1700288571000},"score":1,"resource":{"primary":{"URL":"https:\/\/biosignaling.biomedcentral.com\/articles\/10.1186\/s12964-023-01258-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,21]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["1258"],"URL":"https:\/\/doi.org\/10.1186\/s12964-023-01258-2","relation":{},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,21]]},"assertion":[{"value":"1 June 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 September 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All experiments were conducted in accordance with the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals, and the ARRIVE Guidelines for Reporting Animal Research. All experiments were approved by the Experimental Animal Care and Use Committee of Zhongshan Hospital, Fudan University (Shanghai, China).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"250"}}