Topically injected adrenocorticotropic hormone induces mechanical hypersensitivity on a full-thickness cutaneous wound model in rats.

Abstract

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.

• Authors: Taichi Goto, Gojiro Nakagami, Takeo Minematsu, Sanai Tomida, Masamichi Shinoda, Koichi Iwata, Hiromi Sanada
• Journal: Experimental dermatology (Exp Dermatol) Vol. 28 Issue 9 Pg. 1010-1016 (09 2019) ISSN: 1600-0625 [Electronic] Denmark
• PMID: 31260140 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Ion Channels
• TRPV Cation Channels
• Trpv4 protein, rat
• 5,6-epoxy-8,11,14-eicosatrienoic acid
• Adrenocorticotropic Hormone
• Cytochrome P-450 Enzyme System
• CYP2B12 protein, rat
• 8,11,14-Eicosatrienoic Acid
• Corticosterone

Topics

• 8,11,14-Eicosatrienoic Acid (analogs & derivatives, analysis)
• Adrenocorticotropic Hormone (toxicity)
• Animals
• Corticosterone (biosynthesis)
• Cytochrome P-450 Enzyme System (biosynthesis, genetics)
• Granulation Tissue (drug effects, physiopathology)
• Hyperalgesia (chemically induced, etiology, physiopathology)
• Hypothalamo-Hypophyseal System (physiopathology)
• Ion Channels (drug effects, physiology)
• Male
• Models, Neurological
• Pain (etiology, physiopathology)
• Pain Threshold (drug effects)
• Pituitary-Adrenal System (physiopathology)
• Rats
• Rats, Sprague-Dawley
• Skin (injuries)
• Stress, Psychological (physiopathology)
• TRPV Cation Channels (drug effects, physiology)
• Up-Regulation (drug effects)
• Wound Healing (drug effects)