{"doi":"10.1111/1753-0407.12841","title":"Peripheral pain is enhanced by insulin‐like growth factor 1 and its receptors in a mouse model of type 2 diabetes mellitus","abstract":"<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Insulin‐like growth factor 1 (IGF1) is a neurotrophic factor with many actions, including a possible hyperalgesic effect. This study investigated the effects of IGF1 on the overall behavior of diabetic mice and explored the possible mechanisms underlying IGF1‐induced pain.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Mice were divided into five groups (<jats:italic>db/m</jats:italic>, <jats:italic>db/db</jats:italic>, vehicle‐treated <jats:italic>db/db</jats:italic>, IGF1‐treated <jats:italic>db/db</jats:italic>, and IGF1 + JB1‐treated <jats:italic>db/db</jats:italic> mice). Behavioral studies were conducted using the hot plate and Von Frey tests after intraplantar injection of recombinant (r) IGF1 (50 μg/kg) and the IGF1 receptor (IGF1R) antagonist JB1 (6 μg/mouse). Morphological changes in dorsal root ganglia (DRG) were evaluated using electron microscopy. Immunofluorescence was used to detect IGF1R expression and colocalisation with pain mediators in the DRG. Changes in the expression of IGF1R, extracellular signal‐regulated kinase (ERK), and ras‐associated factor‐1 (c‐raf) in the DRG were evaluated using western blotting.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Intraplantar injection of rIGF1 resulted in a hyperalgesic effect after 2 hours. This IGF1‐induced hypersensitivity was attenuated by prior intraplantar injection of the IGF1R antagonist. There was no significant change in neuronal structure in the <jats:italic>db/m</jats:italic> group, whereas neuronal structure was impaired in the other four groups. Moreover, IGF1R was colocalised with pain mediators in the DRG of mice. Intraplantar injection of rIGF1 resulted in increased IGF1R, phosphorylated (p‐) ERK, and c‐raf expression in the DRG; prior intraplantar injection of the IGF1R antagonist attenuated rIGF1‐induced increases in p‐ERK and c‐raf.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The results indicate that IGF1‐induced acute hyperalgesia may be associated with the IGF1R/c‐raf/ERK pathway. The IGF1‐induced hypersensitivity was attenuated by an IGF1R antagonist.</jats:p></jats:sec>","journal":"Journal of Diabetes","year":2019,"id":602816,"datarank":0.42498200160843247,"base_score":2.833213344056216,"endowment":2.833213344056216,"self_citation_contribution":0.42498200160843247,"citation_network_contribution":0.0,"self_endowment_contribution":0.42498200160843247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"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":1546179,"name":"Fuming Cao","orcid":null,"position":1,"is_corresponding":false},{"id":589699,"name":"Hao Zhang","orcid":"0000-0002-9192-4684","position":2,"is_corresponding":false},{"id":1369304,"name":"Jin Tang","orcid":"0009-0004-7474-5109","position":3,"is_corresponding":false},{"id":1546180,"name":"Huizhi Li","orcid":null,"position":4,"is_corresponding":false},{"id":1374683,"name":"Yiyun Zhang","orcid":"0000-0002-1419-485X","position":5,"is_corresponding":false},{"id":804304,"name":"Bo Feng","orcid":"0000-0001-7815-7137","position":6,"is_corresponding":false},{"id":868721,"name":"Hua Wang","orcid":"0000-0003-2633-3420","position":7,"is_corresponding":false},{"id":1546178,"name":"Zhaosheng Tang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Peripheral pain is enhanced by insulin‐like growth factor 1 and its receptors in a mouse model of type 2 diabetes mellitus","abstract":"<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Insulin‐like growth factor 1 (IGF1) is a neurotrophic factor with many actions, including a possible hyperalgesic effect. This study investigated the effects of IGF1 on the overall behavior of diabetic mice and explored the possible mechanisms underlying IGF1‐induced pain.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Mice were divided into five groups (<jats:italic>db/m</jats:italic>, <jats:italic>db/db</jats:italic>, vehicle‐treated <jats:italic>db/db</jats:italic>, IGF1‐treated <jats:italic>db/db</jats:italic>, and IGF1 + JB1‐treated <jats:italic>db/db</jats:italic> mice). Behavioral studies were conducted using the hot plate and Von Frey tests after intraplantar injection of recombinant (r) IGF1 (50 μg/kg) and the IGF1 receptor (IGF1R) antagonist JB1 (6 μg/mouse). Morphological changes in dorsal root ganglia (DRG) were evaluated using electron microscopy. Immunofluorescence was used to detect IGF1R expression and colocalisation with pain mediators in the DRG. Changes in the expression of IGF1R, extracellular signal‐regulated kinase (ERK), and ras‐associated factor‐1 (c‐raf) in the DRG were evaluated using western blotting.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Intraplantar injection of rIGF1 resulted in a hyperalgesic effect after 2 hours. This IGF1‐induced hypersensitivity was attenuated by prior intraplantar injection of the IGF1R antagonist. There was no significant change in neuronal structure in the <jats:italic>db/m</jats:italic> group, whereas neuronal structure was impaired in the other four groups. Moreover, IGF1R was colocalised with pain mediators in the DRG of mice. Intraplantar injection of rIGF1 resulted in increased IGF1R, phosphorylated (p‐) ERK, and c‐raf expression in the DRG; prior intraplantar injection of the IGF1R antagonist attenuated rIGF1‐induced increases in p‐ERK and c‐raf.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The results indicate that IGF1‐induced acute hyperalgesia may be associated with the IGF1R/c‐raf/ERK pathway. The IGF1‐induced hypersensitivity was attenuated by an IGF1R antagonist.</jats:p></jats:sec>","is_dataset_classified":null,"base_score":2.833213344056216,"endowment":2.833213344056216,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30105862","pmcid":null,"openalex_id":"https://openalex.org/W2887124809","authors":[],"funders":[{"funder_name":"Shanghai Natural Science Foundation of China","grant_id":"14ZR1434000","title":null},{"funder_name":"Science and Technology Development Fund of Shanghai Pudong New Area","grant_id":"PKJ2015-Y19","title":null}],"total_grants":2,"fwci":0.6293,"citation_percentile":0.67412212,"influential_citations":0,"citation_trend":[{"year":2019,"count":1},{"year":2020,"count":4},{"year":2022,"count":2},{"year":2023,"count":7},{"year":2024,"count":2}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2F1753-0407.12841","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/1753-0407.12841","host_type":"publisher"},{"url":"https://doi.org/10.1111/1753-0407.12841","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30105862","host_type":"repository"}],"fields_of_study":["Pain Mechanisms and Treatments","Growth Hormone and Insulin-like Growth Factors","Pregnancy-related medical research","Animals","Diabetes Mellitus, Experimental","Diabetes Mellitus, Type 2","Disease Models, Animal","Extracellular Signal-Regulated MAP Kinases","Hyperalgesia","Insulin-Like Growth Factor I","Male","Mice","Pain","Phosphorylation","Receptor, IGF Type 1","Signal Transduction"],"mesh_terms":["Animals","Diabetes Mellitus, Experimental","Diabetes Mellitus, Type 2","Disease Models, Animal","Hyperalgesia","Insulin-Like Growth Factor I","Male","Pain","Phosphorylation","Signal Transduction","Receptor, IGF Type 1","Extracellular Signal-Regulated MAP Kinases","Mice"],"keywords":["Insulin-like growth factor 1 receptor","Insulin-like growth factor","Medicine","MAPK/ERK pathway","Neurotrophic factors","Endocrinology","Hyperalgesia","Growth factor","Internal medicine","Antagonist","Receptor","Extracellular","Receptor antagonist","Kinase","Nociception","Chemistry","Biochemistry","Diabetes mellitus","Insulin-like growth factor 1","Pain","Dorsal root ganglia","diabetic peripheral neuropathy","糖尿病","糖尿病周围神经病变","疼痛","背根神经节","胰岛素样生长因子1","胰岛素样生长因子1受体"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T20:22:50.518074Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}