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Review
. 2023 Jan 20;24(3):2045.
doi: 10.3390/ijms24032045.

Sympathetic System in Wound Healing: Multistage Control in Normal and Diabetic Skin

Evgenii Ivanov  1 , Marina Akhmetshina  1 , Aleksei Erdiakov  1 , Svetlana Gavrilova  1
Affiliations
Review

Sympathetic System in Wound Healing: Multistage Control in Normal and Diabetic Skin

Evgenii Ivanov et al. Int J Mol Sci. .

Abstract

In this review, we discuss sympathetic regulation in normal and diabetic wound healing. Experimental denervation studies have confirmed that sympathetic nerve endings in skin have an important and complex role in wound healing. Vasoconstrictor neurons secrete norepinephrine (NE) and neuropeptide Y (NPY). Both mediators decrease blood flow and interact with inflammatory cells and keratinocytes. NE acts in an ambiguous way depending on receptor type. Beta2-adrenoceptors could be activated near sympathetic endings; they suppress inflammation and re-epithelialization. Alpha1- and alpha2-adrenoceptors induce inflammation and activate keratinocytes. Sudomotor neurons secrete acetylcholine (ACh) and vasoactive intestinal peptide (VIP). Both induce vasodilatation, angiogenesis, inflammation, keratinocytes proliferation and migration. In healthy skin, all effects are important for successful healing. In treatment of diabetic ulcers, mediator balance could be shifted in different ways. Beta2-adrenoceptors blockade and nicotinic ACh receptors activation are the most promising directions in treatment of diabetic ulcers with neuropathy, but they require further research.

Keywords: NGF; NPY; VIP; acetylcholine; angiogenesis; diabetes mellitus; keratinocytes; norepinephrine; sympathetic system; wound healing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Normal autonomic skin innervation.
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