{"doi":"10.1159/000488624","title":"Increased Asics Expression via the Camkii-CREB Pathway in a Novel Mouse Model of Trigeminal Pain","abstract":"<jats:p>Background/Aims: Migraine is a disabling condition that severely impacts socioeconomic function and quality of life. The focus of this study was to develop a mouse model of trigeminal pain that mimics migraine. Methods: After undergoing dural cannulation surgery, mice were treated with repeated dural doses of an acidic solution to induce trigeminal pain. Results: The method elicited intermittent, head-directed wiping and scratching as well as the expression of both the c-FOS gene in the spinal trigeminal nucleus caudalis and calcitonin gene related peptide (CGRP) in the periaqueductal grey matter. Interestingly, the acid-induced trigeminal pain behaviour was inhibited by amiloride, an antagonist of acid-sensing ion channels (ASICs), but not by AMG-9810, an inhibitor of transient receptor potential cation channel V1(TRPV1). In addition, the relative mRNA and protein expression levels of ASIC1a and ASIC3 were increased in the acid-induced trigeminal nociceptive pathways. Furthermore, blocking CaMKII with KN-93 significantly reduced the acid-induced trigeminal pain behaviour and c-FOS gene expression. Conclusion: The data suggested that chronic intermittent administration of an acidic solution to mice resulted in trigeminal hypersensitivity and that dural acid-induced trigeminal pain behaviour in mice may mechanistically mimic migraine. The observations here identify an entirely novel treatment strategy for migraine.</jats:p>","journal":"Cellular Physiology and Biochemistry","year":2018,"id":31661,"datarank":0.7859002437346309,"base_score":3.4339872044851463,"endowment":3.4339872044851463,"self_citation_contribution":0.515098080672772,"citation_network_contribution":0.2708021630618589,"self_endowment_contribution":0.515098080672772,"citer_contribution":0.2708021630618589,"corpus_percentile":null,"corpus_rank":null,"citation_count":30,"citer_count":9,"citers_with_citation_signal":8,"citers_with_endowment":8,"datacite_reuse_total":20,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":169196,"name":"Xiujuan Fu","orcid":null,"position":1,"is_corresponding":false},{"id":169197,"name":"Lifang Huang","orcid":null,"position":2,"is_corresponding":false},{"id":17706,"name":"Xi Wang","orcid":"0000-0002-4660-9562","position":3,"is_corresponding":false},{"id":169198,"name":"Zuneng Lu","orcid":null,"position":4,"is_corresponding":false},{"id":27471,"name":"Fan Zhu","orcid":"0009-0007-2339-9084","position":5,"is_corresponding":false},{"id":169199,"name":"Zheman Xiao","orcid":null,"position":6,"is_corresponding":false},{"id":3711,"name":"Yan Wang","orcid":"0000-0003-2563-255X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.4339872044851463,"endowment":3.4339872044851463,"datacite_reuse_total":20,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"29617678","pmcid":null,"openalex_id":"https://openalex.org/W2795545682","authors":[],"funders":[],"total_grants":0,"fwci":0.4783,"citation_percentile":0.64701703,"influential_citations":1,"citation_trend":[{"year":2020,"count":2},{"year":2021,"count":1},{"year":2022,"count":18},{"year":2023,"count":2},{"year":2024,"count":6},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.karger.com/Article/Pdf/488624","host_type":"journal"},{"url":"https://www.karger.com/Article/Pdf/488624","host_type":"GOLD"},{"url":"https://www.karger.com/Article/Pdf/488624","host_type":"publisher"},{"url":"https://doi.org/10.1159/000488624","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/29617678","host_type":"repository"},{"url":"https://doaj.org/article/0da5a196832242f9853440f692f851af","host_type":"repository"}],"fields_of_study":["Migraine and Headache Studies","Pain Mechanisms and Treatments","Neuroscience of respiration and sleep","Medicine","Acetic Acid","Acid Sensing Ion Channel Blockers","Acid Sensing Ion Channels","Acrylamides","Amiloride","Animals","Behavior, Animal","Bridged Bicyclo Compounds, Heterocyclic","Calcitonin Gene-Related Peptide","Calcium-Calmodulin-Dependent Protein Kinase Type 2","Cyclic AMP Response Element-Binding Protein","Disease Models, Animal","Male","Mice","Mice, Inbred C57BL","Pain","Phosphorylation","Proto-Oncogene Proteins c-fos","TRPV Cation Channels","Trigeminal Nucleus, Spinal"],"mesh_terms":["Acrylamides","Amiloride","Animals","Behavior, Animal","Disease Models, Animal","Male","Mice, Inbred C57BL","Pain","Phosphorylation","Trigeminal Nucleus, Spinal","Calcitonin Gene-Related Peptide","Proto-Oncogene Proteins c-fos","Cyclic AMP Response Element-Binding Protein","Bridged Bicyclo Compounds, Heterocyclic","Acetic Acid","TRPV Cation Channels","Mice","Calcium-Calmodulin-Dependent Protein Kinase Type 2","Acid Sensing Ion Channels","Acid Sensing Ion Channel Blockers"],"keywords":["Calcitonin gene-related peptide","TRPV1","Nociceptor","Spinal trigeminal nucleus","Trigeminal ganglion","Nociception","Transient receptor potential channel","Medicine","Migraine","Pharmacology","Trigeminal neuralgia","Acid-sensing ion channel","Trigeminal nerve","Anesthesia","Chemistry","Endocrinology","Receptor","Internal medicine","Neuroscience","Neuropeptide","Ion channel","Biology","c-fos gene","Asics","Trigeminal Pain","Camkii-creb"],"sdg_mappings":[],"linked_datasets":[{"doi":"10.6084/m9.figshare.26687579.v1","title":"Additional file 1 of AMPK activation attenuates central sensitization in a recurrent nitroglycerin-induced chronic migraine mouse model by promoting microglial M2-type polarization","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.26687579","title":"Additional file 1 of AMPK activation attenuates central sensitization in a recurrent 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