Topically injected adrenocorticotropic hormone induces mechanical hypersensitivity on a full-thickness cutaneous wound model in rats
Taichi Goto
Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Global Leadership Initiative for an Age-Friendly Society, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorGojiro Nakagami
Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Division of Care Innovation, Global Nursing Research Center, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorTakeo Minematsu
Division of Care Innovation, Global Nursing Research Center, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Department of Skincare Science, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorSanai Tomida
Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorMasamichi Shinoda
Department of Physiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan
Search for more papers by this authorKoichi Iwata
Department of Physiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Hiromi Sanada
Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Division of Care Innovation, Global Nursing Research Center, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Correspondence
Hiromi Sanada, Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Email: [email protected]
Search for more papers by this authorTaichi Goto
Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Global Leadership Initiative for an Age-Friendly Society, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorGojiro Nakagami
Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Division of Care Innovation, Global Nursing Research Center, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorTakeo Minematsu
Division of Care Innovation, Global Nursing Research Center, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Department of Skincare Science, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorSanai Tomida
Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Search for more papers by this authorMasamichi Shinoda
Department of Physiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan
Search for more papers by this authorKoichi Iwata
Department of Physiology, Nihon University School of Dentistry, Chiyoda-ku, Tokyo, Japan
Search for more papers by this authorCorresponding Author
Hiromi Sanada
Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Division of Care Innovation, Global Nursing Research Center, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
Correspondence
Hiromi Sanada, Department of Gerontological Nursing/Wound Care Management, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Email: [email protected]
Search for more papers by this authorAbstract
Cutaneous wound pain causes physical and psychological stress for patients with wounds. Previous studies reported that stress induces hyperalgesia and deteriorates wound healing. However, the effect of the stress response such as in hypothalamic-pituitary-adrenal (HPA) axis on local wound area is unclear. We aimed to investigate the effects of a stress response on the mechanical withdrawal threshold in the local wound area and describe the identification of a wound pain exacerbation. We topically injected adrenocorticotropic hormone (ACTH) into the granulation tissue of full-thickness cutaneous wound model rats on the fifth day postwounding and measured the mechanical withdrawal thresholds, cytochrome P450 2Bs levels and concentration of 5,6-epoxyeicosatrienoic acid in wound exudate. We found that ACTH induced mechanical hypersensitivity at 4 and 6 hours after injection (P = .004 and .021, respectively), and increased gene expression of cytochrome P450 2B12 expression (P = .046). Concentration of 5,6-EET in the wound exudate was moderately correlated with the mechanical withdrawal threshold (r = −.630). Finally, the mechanical withdrawal threshold in the 5,6-EET group was significantly lower than that in the control group at 2 hours after the injection (P = .015). We propose that 5,6-EET is one of the most promising contributors to the wound pain exacerbation. These findings could guide clinical wound and pain management.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest.
Supporting Information
| Filename | Description |
|---|---|
| exd13994-sup-0001-FigS1.tiffTIFF image, 2.1 MB | Fig. S1. The comparison of the wound area between the control and corticosterone groups just before treatment. |
| exd13994-sup-0002-FigS2.tiffTIFF image, 2.1 MB | Fig. S2. The comparison of the wound area between the control and ACTH groups just before treatment. |
| exd13994-sup-0003-FigS3.tiffTIFF image, 2.1 MB | Fig. S3. The presence of TRPV4 at the epidermis of peri wound skin. |
| exd13994-sup-0004-FigS4.tiffTIFF image, 2.1 MB | Fig. S4. The presence of TRPV4 at the granulation tissue. |
| exd13994-sup-0005-FigS5.tiffTIFF image, 2.1 MB | Fig. S5. The comparison of the wound area between the control and ACTH groups just before treatment. |
| exd13994-sup-0006-FigS6.tiffTIFF image, 2.1 MB | Fig. S6. The mechanical withdrawal threshold changes between the control and ACTH groups. |
| exd13994-sup-0007-FigS7.tiffTIFF image, 2.1 MB | Fig. S7. Western blotting analyses for ACTH-induced protein kinase C and protein kinase A in the surrounding skin tissue. |
| exd13994-sup-0008-FigS8.tiffTIFF image, 2.1 MB | Fig. S8. Real-time reverse transcription polymerase chain reaction analyses for ACTH-regulated Cyp expressions in the surrounding skin tissue. |
| exd13994-sup-0009-FigS9.tiffTIFF image, 2.1 MB | Fig. S9. The comparison of the wound area between the control and 5.6-EET groups just before treatment. |
| exd13994-sup-0010-AppendixS1.docxapplication/docx, 40 KB | Appendix S1. Materials and methods. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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