Interleukin-10 Reduces Neurogenic Inflammation and Pain Behavior in a Mouse Model of Type 2 Diabetes
| Autor: | Jacqueline R. Dauch, Brandon M. Yanik, Hsinlin T. Cheng |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
dorsal root ganglion medicine.medical_treatment Inflammation 03 medical and health sciences 0302 clinical medicine 030202 anesthesiology Internal medicine painful diabetic neuropathy cytokine medicine Langerhans cells Journal of Pain Research Original Research Neurogenic inflammation business.industry Interleukin Interleukin 10 Anesthesiology and Pain Medicine Nerve growth factor Cytokine Endocrinology Neuropathic pain Tumor necrosis factor alpha type 2 diabetes medicine.symptom business 030217 neurology & neurosurgery |
| Zdroj: | Journal of Pain Research |
| ISSN: | 1178-7090 |
| DOI: | 10.2147/jpr.s264136 |
| Popis: | Brandon M Yanik,1 Jacqueline R Dauch,1 Hsinlin T Cheng1,2 1Department of Neurology, University of Michigan Medical Center, Ann Arbor, Michigan, USA; 2Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USACorrespondence: Hsinlin T ChengMassachusetts General Hospital, Harvard Medical School, WACC 835, 55 Fruit Street, Boston, MA 02114, USATel +1 2 617-724-6213Fax +1 2 617-724-0895Email htcheng@mgh.harvard.eduPurpose: 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.Keywords: dorsal root ganglion, painful diabetic neuropathy, cytokine, Langerhans cells, type 2 diabetes |
| Databáze: | OpenAIRE |
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