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Nociceptive and Transcriptomic Responses in a Swine Diabetic Wound Model Treated With a Topical Angiotensin 1
Background:
Painful, treatment-resistant wounds are prevalent among diabetic patients and significantly affect health-related quality of life (HRQOL). Topical treatments may help alleviate pain without risk of dependence or side effects. However, there is a lack of topical wound compounds targeting pain-specific receptors. One possible target is proinflammatory angiotensin 1 receptor (AT1R), which is upregulated in diabetic skin and has been implicated in nociception.
Objectives:
We investigated the effects of topical valsartan, an AT1R antagonist, on pain (nociceptive thresholds) and gene expression changes (transcriptomics) in a swine model of diabetic wounds.
Methods:
Eight wounds were surgically induced in diabetic, hyperglycemic Yucatan miniature swine ( n = 4). Topical AT1R antagonist was applied to wounds on one side and vehicle on the other side. Nocifensive testing was conducted at baseline and then weekly, beginning 7 days after wound induction. Mechanical and thermal stimuli were applied to the wound margins until a nocifensive reaction was elicited or a predetermined cutoff was reached. After 7 weeks of testing, tissue from the dorsal horn, dorsal root ganglion, and wounds were sequenced and analyzed with DESeq2. Unbiased pathway analyses using Metascape were conducted on differentially expressed genes.
Results:
There was no significant difference in mechanical tolerance threshold between AT1R antagonist-treated and vehicle-treated wounds ( p = .106). Thermal tolerance was significantly higher in AT1R antagonist-treated wounds compared to vehicle-treated ( p = .015). Analysis of differentially expressed genes revealed enriched pathways of interest: interleukin-18 signaling in dorsal horn laminae IV-V and sensory perception of mechanical stimulus in wound tissue.
Discussion:
In this study, wounds modeling diabetic ulcers were created in hyperglycemic swine and treated with a topical AT1R antagonist. AT1R-antagonist-treated wounds had a higher tolerance threshold than vehicle-treated wounds for thermal hyperalgesia, but not mechanical allodynia. Pathway analyses of differentially expressed genes revealed several pathways of interest for future pain research. Although further studies are needed to confirm the findings, this study can improve nursing care by providing information about a potential future treatment that may be used to decrease pain and improve HRQOL in patients with diabetic wounds.
Insights
Topical valsartan, an angiotensin 1 receptor (AT1R) antagonist, improved thermal pain tolerance in diabetic swine wounds. This suggests a potential new treatment to reduce pain and enhance quality of life for diabetic patients with chronic wounds.
Area of Science:
- Biomedical research
- Wound healing
- Pain management
Background:
- Diabetic wounds cause significant pain and reduced quality of life.
- Current topical treatments lack pain-specific receptor targets.
- Angiotensin 1 receptor (AT1R) is upregulated in diabetic skin and linked to pain.
Purpose of the Study:
- To evaluate topical valsartan's effect on pain and gene expression in diabetic swine wounds.
- To investigate valsartan as a potential treatment for diabetic wound pain.
Main Methods:
- Diabetic swine underwent wound induction; topical AT1R antagonist (valsartan) or vehicle was applied.
- Nocifensive testing (mechanical and thermal) was performed weekly.
- Tissue transcriptomics and pathway analysis were conducted.
Main Results:
- Topical AT1R antagonist significantly increased thermal pain tolerance.
- No significant difference in mechanical pain tolerance was observed.
- Gene expression analysis identified enriched pathways related to inflammation and pain signaling.
Conclusions:
- Topical AT1R antagonism shows promise for managing thermal hyperalgesia in diabetic wounds.
- Further research is needed to confirm findings and explore therapeutic potential.
- This approach may improve pain management and quality of life for diabetic patients.
