Peripheral pain is enhanced by insulin-like growth factor 1 and its receptors in a mouse model of type 2 diabetes mellitus.

Journal of diabetes [J Diabetes] 2019 Apr; Vol. 11 (4), pp. 309-315. Date of Electronic Publication: 2018 Sep 23.

Background: 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.
Methods: Mice were divided into five groups (db/m, db/db, vehicle-treated db/db, IGF1-treated db/db, and IGF1 + JB1-treated db/db 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.
Results: 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 db/m 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.
Conclusions: 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.
(© 2018 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

English

Publisher: Blackwell Publishing Asia Country of Publication: Australia NLM ID: 101504326 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1753-0407 (Electronic) Linking ISSN: 17530407 NLM ISO Abbreviation: J Diabetes Subsets: MEDLINE

Disease Models, Animal*, Diabetes Mellitus, Experimental/*complications , Diabetes Mellitus, Type 2/*complications , Hyperalgesia/*etiology , Insulin-Like Growth Factor I/*adverse effects , Pain/*etiology , Receptor, IGF Type 1/*adverse effects, Animals ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/pathology ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Hyperalgesia/metabolism ; Hyperalgesia/pathology ; Insulin-Like Growth Factor I/administration & dosage ; Insulin-Like Growth Factor I/metabolism ; Male ; Mice ; Pain/metabolism ; Pain/pathology ; Phosphorylation ; Receptor, IGF Type 1/administration & dosage ; Receptor, IGF Type 1/metabolism ; Signal Transduction

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