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Recent studies recapitulate the spinal neurocircuits associated with neuroinflammation and synaptic plasticity responsible for pruriceptive sensations. The resolution of nociception and inflammation by Annexin 1 (ANXA1) has been identified. Given that pain and itch share many neural mechanisms, we employed two mice models of chronic itch to study the underlying targets and therapeutic potential of ANXA1, comprising allergic contact dermatitis-induced itch and cholestatic itch. Herein, we report that spinal expression of ANXA1 is down-regulated in mice with dermatitis-induced itch and cholestatic itch. Repetitive injections of ANXA1-derived peptide Ac2-26 (intrathecal, 10 \u03bcg) reduce itch-like scratching behaviors following dermatitis and cholestasis. Single exposure to Ac2-26 (intrathecal, 10 \u03bcg) alleviates the established itch phenotypes. Moreover, systemic delivery of Ac2-26 (intravenous, 100 \u03bcg) is effective against chronic dermatitis-induced itch and cholestatic itch. Strikingly, Ac2-26 therapy inhibits transferrin receptor 1 over-expression, iron accumulation, cytokine IL-17 release and the production of its receptor IL-17R, as well as astrocyte activation in the dorsal horn of spinal cord in mouse with dermatitis and cholestasis. Pharmacological intervention with iron chelator deferoxamine impairs chronic itch behaviors and spinal iron accumulation after dermatitis and cholestasis. Also, spinal IL-17\/IL-17R neutralization attenuates chronic itch. Taken together, this current research indicates that ANXA1 protects against the beginning and maintenance of long-term dermatitis-induced itch and cholestatic itch, which may occur via the spinal suppression of IL-17-mediated neuroinflammation, astrocyte activation and iron overload.<\/jats:p>","DOI":"10.3390\/brainsci14050440","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T09:50:07Z","timestamp":1714470607000},"page":"440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Annexin 1 Reduces Dermatitis-Induced Itch and Cholestatic Itch through Inhibiting Neuroinflammation and Iron Overload in the Spinal Dorsal Horn of Mice"],"prefix":"10.3390","volume":"14","author":[{"given":"Tang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Pain Research Center, The Affiliated Hospital of Jiaxing University, Jiaxing 314001, China"},{"name":"Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingyue","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanjie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenhua","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2644-4289","authenticated-orcid":false,"given":"Linlin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1152\/physrev.00017.2019","article-title":"Physiology and pathophysiology of itch","volume":"100","author":"Cevikbas","year":"2020","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jaad.2021.07.076","article-title":"Itch: Epidemiology, clinical presentation, and diagnostic workup","volume":"86","author":"Roh","year":"2022","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41575-022-00687-7","article-title":"Mechanisms of pruritus in cholestasis: Understanding and treating the itch","volume":"20","author":"Beuers","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4775","DOI":"10.1111\/bph.15672","article-title":"Chronic itch: Emerging treatments following new research concepts","volume":"178","author":"Misery","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1016\/j.jaip.2020.12.007","article-title":"Sleep disturbances and atopic dermatitis: Relationships, methods for assessment, and therapies","volume":"9","author":"Bawany","year":"2021","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1111\/exd.13992","article-title":"What is new in the psychology of chronic itch?","volume":"28","author":"Evers","year":"2019","journal-title":"Exp. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/s41583-019-0218-1","article-title":"Astrocytes in chronic pain and itch","volume":"20","author":"Ji","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1097\/j.pain.0000000000002824","article-title":"Novel proresolving lipid mediator mimetic 3-oxa-PD1n-3 docosapentaenoic acid reduces acute and chronic itch by modulating excitatory and inhibitory synaptic transmission and astroglial secretion of lipocalin-2 in mice","volume":"164","author":"Furutani","year":"2023","journal-title":"PAIN"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.neures.2022.09.013","article-title":"IP3R1-dependent astrocyte calcium signaling in chronic itch","volume":"187","author":"Tsuda","year":"2023","journal-title":"Neurosci. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/nm.3912","article-title":"STAT3-dependent reactive astrogliosis in the spinal dorsal horn underlies chronic itch","volume":"21","author":"Koga","year":"2015","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"805222","DOI":"10.3389\/fphar.2021.805222","article-title":"Paeonol ameliorates chronic itch and spinal astrocytic activation via CXCR3 in an experimental dry skin model in mice","volume":"12","author":"Wang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"999407","DOI":"10.3389\/fimmu.2022.999407","article-title":"Interleukin-17 as a potential therapeutic target for chronic pain","volume":"13","author":"Jiang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pang, J., Xin, P., Kong, Y., Wang, Z., and Wang, X. (2023). Resolvin D2 reduces chronic neuropathic pain and bone cancer pain via spinal inhibition of IL-17 secretion, CXCL1 release and astrocyte activation in mice. Brain Sci., 13.","DOI":"10.3390\/brainsci13010152"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/jcp.30923","article-title":"Keratinocyte TLR2 and TLR7 contribute to chronic itch through pruritic cytokines and chemokines in mice","volume":"238","author":"Wang","year":"2023","journal-title":"J. Cell. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.neulet.2018.12.001","article-title":"The involvement of iron responsive element (-) divalent metal transporter 1-mediated the spinal iron overload via CXCL10\/CXCR3 pathway in neuropathic pain in rats","volume":"694","author":"Xu","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1097\/j.pain.0000000000002021","article-title":"Spinal caspase-6 regulates AMPA receptor trafficking and dendritic spine plasticity through netrin-1 in postoperative pain after orthopedic surgery for tibial fracture in mice","volume":"162","author":"Cui","year":"2021","journal-title":"PAIN"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, Y., Wang, P., Liu, C., Chen, W., Wang, P., and Jiang, L. (2022). Hydrogen-rich saline attenuates chronic allodynia after bone fractures via reducing spinal CXCL1\/CXCR2-mediated iron accumulation in mice. Brain Sci., 12.","DOI":"10.3390\/brainsci12121610"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5561","DOI":"10.7150\/thno.85390","article-title":"Tat-NTS peptide protects neurons against cerebral ischemia-reperfusion injury via ANXA1 SUMOylation in microglia","volume":"13","author":"Zhou","year":"2023","journal-title":"Theranostics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1002\/jnr.24478","article-title":"Annexin A1 attenuates neuroinflammation through FPR2\/p38\/COX-2 pathway after intracerebral hemorrhage in male mice","volume":"98","author":"Ding","year":"2020","journal-title":"J. Neurosci. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1002\/j.1532-2149.2013.00373.x","article-title":"Annexin 1: A glucocorticoid-inducible protein that modulates inflammatory pain","volume":"18","author":"Chen","year":"2014","journal-title":"Eur. J. Pain"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.neures.2018.07.007","article-title":"Annexin 1 inhibits remifentanil-induced hyperalgesia and NMDA receptor phosphorylation via regulating spinal CXCL12\/CXCR4 in rats","volume":"144","author":"Li","year":"2019","journal-title":"Neurosci. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1093\/bja\/aer299","article-title":"Annexin 1 exerts anti-nociceptive effects after peripheral inflammatory pain through formyl-peptide-receptor-like 1 in rat dorsal root ganglion","volume":"107","author":"Pei","year":"2011","journal-title":"Br. J. Anaesth."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/s41586-020-03151-1","article-title":"STING controls nociception via type I interferon signalling in sensory neurons","volume":"591","author":"Donnelly","year":"2021","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1093\/brain\/awaa430","article-title":"Central opioid receptors mediate morphine-induced itch and chronic itch via disinhibition","volume":"144","author":"Wang","year":"2021","journal-title":"Brain"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/s12264-017-0128-z","article-title":"Chemokine receptor CXCR3 in the spinal cord contributes to chronic itch in mice","volume":"34","author":"Jing","year":"2018","journal-title":"Neurosci. Bull."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1248\/bpb.b20-00097","article-title":"Pharmacological characterization of a novel mouse model of cholestatic pruritus","volume":"43","author":"Andoh","year":"2020","journal-title":"Biol. Pharm. Bull."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1136\/rapm-2020-101883","article-title":"Spinal NR2B phosphorylation at Tyr1472 regulates IRE(\u2212)DMT1-mediated iron accumulation and spine morphogenesis via kalirin-7 in tibial fracture-associated postoperative pain after orthopedic surgery in female mice","volume":"46","author":"Zhang","year":"2021","journal-title":"Reg. Anesth. Pain Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.neuron.2018.03.023","article-title":"Peripheral and central mechanisms of itch","volume":"98","author":"Dong","year":"2018","journal-title":"Neuron"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41586-022-04860-5","article-title":"PIEZO1 transduces mechanical itch in mice","volume":"607","author":"Hill","year":"2022","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1272230","DOI":"10.3389\/fnmol.2023.1272230","article-title":"Itch: From the skin to the brain\u2014Peripheral and central neural sensitization in chronic itch","volume":"16","author":"Mahmoud","year":"2023","journal-title":"Front. Mol. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s12974-023-02783-0","article-title":"STING controls opioid-induced itch and chronic itch via spinal tank-binding kinase 1-dependent type I interferon response in mice","volume":"20","author":"Li","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1038\/s42255-023-00756-4","article-title":"Loss of fatty acid degradation by astrocytic mitochondria triggers neuroinflammation and neurodegeneration","volume":"5","author":"Mi","year":"2023","journal-title":"Nat. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1038\/s41593-021-00905-6","article-title":"Neuroinflammatory astrocyte subtypes in the mouse brain","volume":"24","author":"Hasel","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/s41422-021-00479-9","article-title":"Single-cell transcriptomic analysis of somatosensory neurons uncovers temporal development of neuropathic pain","volume":"31","author":"Wang","year":"2021","journal-title":"Cell Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/s12974-023-02835-5","article-title":"SAFit2 ameliorates paclitaxel-induced neuropathic pain by reducing spinal gliosis and elevating pro-resolving lipid mediators","volume":"20","author":"Wedel","year":"2023","journal-title":"J. Neuroinflamm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.1016\/j.celrep.2019.10.085","article-title":"Interleukin-17 regulates neuron-glial communications, synaptic transmission, and neuropathic pain after chemotherapy","volume":"29","author":"Luo","year":"2019","journal-title":"Cell Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s12974-021-02174-3","article-title":"Annexin A1 protects against cerebral ischemia-reperfusion injury by modulating microglia\/macrophage polarization via FPR2\/ALX-dependent AMPK-mTOR pathway","volume":"18","author":"Xu","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"eabc5539","DOI":"10.1126\/sciadv.abc5539","article-title":"Annexin-A1 SUMOylation regulates microglial polarization after cerebral ischemia by modulating IKK\u03b1 stability via selective autophagy","volume":"7","author":"Li","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"856254","DOI":"10.3389\/fimmu.2022.856254","article-title":"Annexin-A1 tripeptide attenuates surgery-induced neuroinflammation and memory deficits through regulation the NLRP3 inflammasome","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e00680-20","DOI":"10.1128\/IAI.00680-20","article-title":"Annexin A1 attenuates neutrophil migration and IL-6 expression through Fpr2 in a mouse model of streptococcus suis-induced meningitis","volume":"89","author":"Ni","year":"2021","journal-title":"Infect. Immun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12974-019-1414-7","article-title":"Annexin A1-derived peptide Ac2-26 in a pilocarpine-induced status epilepticus model: Anti-inflammatory and neuroprotective effects","volume":"16","author":"Gimenes","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/s12974-020-01777-6","article-title":"Iron overload contributes to general anaesthesia-induced neurotoxicity and cognitive deficits","volume":"17","author":"Wu","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.brainresbull.2019.12.011","article-title":"Molecular targets and therapeutic interventions for iron induced neurodegeneration","volume":"156","author":"Kaur","year":"2020","journal-title":"Brain Res. Bull."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Feng, Z., Min, L., Chen, H., Deng, W., Tan, M., Liu, H., and Hou, J. (2021). Iron overload in the motor cortex induces neuronal ferroptosis following spinal cord injury. Redox Biol., 43.","DOI":"10.1016\/j.redox.2021.101984"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.jpain.2020.03.007","article-title":"NMDA Receptor Modulates Spinal Iron Accumulation Via Activating DMT1(-)IRE in Remifentanil-Induced Hyperalgesia","volume":"22","author":"Shu","year":"2021","journal-title":"J. Pain"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1097\/ALN.0000000000000562","article-title":"Spinal peroxynitrite contributes to remifentanil-induced postoperative hyperalgesia via enhancement of divalent metal transporter 1 without iron-responsive element-mediated iron accumulation in rats","volume":"122","author":"Shu","year":"2015","journal-title":"Anesthesiology"}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/5\/440\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:35:32Z","timestamp":1760106932000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/5\/440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,28]]},"references-count":46,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["brainsci14050440"],"URL":"https:\/\/doi.org\/10.3390\/brainsci14050440","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,28]]}}}