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Interleukin-10 Reduces Neurogenic Inflammation and Pain Behavior in a Mouse Model of Type 2 Diabetes
PURPOSE: Neurogenic inflammation is a major component of chronic neuropathic pain. Previously, we established the db/db mouse as an animal model of painful diabetic neuropathy (PDN) of type 2 diabetes. In the current study, we investigate the roles of interleukin (IL)-10, an anti-inflammatory cytoki...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Dove
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778525/ https://www.ncbi.nlm.nih.gov/pubmed/33402846 http://dx.doi.org/10.2147/JPR.S264136 |
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author | Yanik, Brandon M Dauch, Jacqueline R Cheng, Hsinlin T |
author_facet | Yanik, Brandon M Dauch, Jacqueline R Cheng, Hsinlin T |
author_sort | Yanik, Brandon M |
collection | PubMed |
description | PURPOSE: Neurogenic inflammation is a major component of chronic neuropathic pain. Previously, we established the db/db mouse as an animal model of painful diabetic neuropathy (PDN) of type 2 diabetes. In the current study, we investigate the roles of interleukin (IL)-10, an anti-inflammatory cytokine, in the development of neurogenic inflammation and pain behavior in db/db mouse. MATERIALS AND METHODS: We first studied IL-10 expression in lumbar dorsal root ganglion (LDRG) neurons of db/db mice using immunohistochemistry, immunoblots, and reverse transcription polymerase chain reaction during the period of pain behavior (from 8 to 16 wk of age). To determine if the reduced IL-10 expression mediates the mechanical allodynia in db/db mice, we administered recombinant mouse IL-10 or saline (control) intraperitoneally to control db/+ and db/db mice starting at 8 wk of age. IL-10 treatment was repeated every other day for 2 wk until the mice reached 10 wk of age. RESULTS: During the period of pain behavior, reduction of IL-10 protein and gene expression was detected in LDRG of db/db mice. Treatment with recombinant IL-10, from 8 to 10 wk of age, alleviates pain behaviors in db/db mice without affecting other diabetic parameters. In parallel, IL-10 treatment reduced the upregulation of nerve growth factor (NGF), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, and high-affinity NGF receptor (Trk A) in LDRG, as well as the numbers of iNOS-positive Langerhans cells and CD-68-positive dermal dendritic cells in the hind-foot-pad skin in db/db mice. CONCLUSION: Our findings suggest that the reduction in neuronal IL-10 increases inflammatory phenomena, ultimately contributing to PDN. These results suggest that the dysregulation of cytokine-mediated inflammation contributes to the development of PDN in db/db mice. Targeting this pathophysiologic mechanism could be an effective approach for treating PDN in type 2 diabetes. |
format | Online Article Text |
id | pubmed-7778525 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-77785252021-01-04 Interleukin-10 Reduces Neurogenic Inflammation and Pain Behavior in a Mouse Model of Type 2 Diabetes Yanik, Brandon M Dauch, Jacqueline R Cheng, Hsinlin T J Pain Res Original Research PURPOSE: Neurogenic inflammation is a major component of chronic neuropathic pain. Previously, we established the db/db mouse as an animal model of painful diabetic neuropathy (PDN) of type 2 diabetes. In the current study, we investigate the roles of interleukin (IL)-10, an anti-inflammatory cytokine, in the development of neurogenic inflammation and pain behavior in db/db mouse. MATERIALS AND METHODS: We first studied IL-10 expression in lumbar dorsal root ganglion (LDRG) neurons of db/db mice using immunohistochemistry, immunoblots, and reverse transcription polymerase chain reaction during the period of pain behavior (from 8 to 16 wk of age). To determine if the reduced IL-10 expression mediates the mechanical allodynia in db/db mice, we administered recombinant mouse IL-10 or saline (control) intraperitoneally to control db/+ and db/db mice starting at 8 wk of age. IL-10 treatment was repeated every other day for 2 wk until the mice reached 10 wk of age. RESULTS: During the period of pain behavior, reduction of IL-10 protein and gene expression was detected in LDRG of db/db mice. Treatment with recombinant IL-10, from 8 to 10 wk of age, alleviates pain behaviors in db/db mice without affecting other diabetic parameters. In parallel, IL-10 treatment reduced the upregulation of nerve growth factor (NGF), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, and high-affinity NGF receptor (Trk A) in LDRG, as well as the numbers of iNOS-positive Langerhans cells and CD-68-positive dermal dendritic cells in the hind-foot-pad skin in db/db mice. CONCLUSION: Our findings suggest that the reduction in neuronal IL-10 increases inflammatory phenomena, ultimately contributing to PDN. These results suggest that the dysregulation of cytokine-mediated inflammation contributes to the development of PDN in db/db mice. Targeting this pathophysiologic mechanism could be an effective approach for treating PDN in type 2 diabetes. Dove 2020-12-29 /pmc/articles/PMC7778525/ /pubmed/33402846 http://dx.doi.org/10.2147/JPR.S264136 Text en © 2020 Yanik et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Yanik, Brandon M Dauch, Jacqueline R Cheng, Hsinlin T Interleukin-10 Reduces Neurogenic Inflammation and Pain Behavior in a Mouse Model of Type 2 Diabetes |
title | Interleukin-10 Reduces Neurogenic Inflammation and Pain Behavior in a Mouse Model of Type 2 Diabetes |
title_full | Interleukin-10 Reduces Neurogenic Inflammation and Pain Behavior in a Mouse Model of Type 2 Diabetes |
title_fullStr | Interleukin-10 Reduces Neurogenic Inflammation and Pain Behavior in a Mouse Model of Type 2 Diabetes |
title_full_unstemmed | Interleukin-10 Reduces Neurogenic Inflammation and Pain Behavior in a Mouse Model of Type 2 Diabetes |
title_short | Interleukin-10 Reduces Neurogenic Inflammation and Pain Behavior in a Mouse Model of Type 2 Diabetes |
title_sort | interleukin-10 reduces neurogenic inflammation and pain behavior in a mouse model of type 2 diabetes |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778525/ https://www.ncbi.nlm.nih.gov/pubmed/33402846 http://dx.doi.org/10.2147/JPR.S264136 |
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