During my research in cutaneous wound healing in diabetics, I observed that the GAP-43 positive nerve fibers increased with the increase in the blood vessels number. Also, the distribution of nerves was more in the blood vessels than other part in granulation tissue. Also the vessels had a larger sized lumen.
The vessels in the granulation tissue, which are having good nerve supply may have large lumen. This may be due to the release of the neurotransmitter, acetylcholine, which has vasodilatory effect on the blood vessels due to the NO production.
Nerve fibers release neuropeptides such as Substance P and CGRP that are highly effective to induce vasodilatation. Neuropeptides are also pro-angiogenic, but during wound healing, inflammation may be more effective to modulate angiogenesis.
See the review by Brant Weinstein published in Cell, Vol. 120, 299–302, February 11, 2005, Copyright ©2005 by Elsevier Inc. DOI 10.1016/j.cell.2005.01.010
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Vessels and Nerves:
Marching to the Same Tune
Brant M. Weinstein
Hi, great discussion and good references. Ingrowth of nerves and vessels go totgether in tendon healing, a tissue normally devoid of nerves and vessels. Opposite to the reference above on cornea nerves and neovessels seem to co-exist in tendon healing, also in pathology, i.e. tendinopathy. See, Ackermann PW. Neuronal regulation of tendon homoeostasis. Int J Exp Pathol. 2013
in cutaneous wound healing, i observed that vessels were well surrounded by the nerve fibers and as the wound get healed the number of blood vessels get decreased in number, which was probably due to apoptosis and remodeling. So, the number of nerves were also decreased in number.
Colleagues in my lab actually found decrease in wound epidermal reinnervation in diabetics. Please see http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0075877
i also observed decreased GAP-43 positive nerve fibers in diabetes, but that was only up to certain period of time. As, after proper wound healing in treatment group of diabetics, the number of nerves decrease with the decline in no. of vessels due to remodeling phase of healing. So, there was not significant difference in the number of nerves in diabetic control and treatment in the latter phase of healing.
Nerve reinnervation during tissue healing seems to be critical during the early inflammatory healing phase, possibly to have a trophic effect by eg. guiding stem cell ingrowth. After the proliferative phase nerve retraction seems to be likewise important for the remodeling phase to progress. What can we do to improve nerve plasticity, i.e. nerve ingrowth and retraction in diabetic patients?
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