Wound Healing in Denervated Tissue

Abstract

Sacral and trochanteric pressure sores in patients with plegias, and foot ulceration in patients with diabetic neuropathy, are similar because these wounds occur in tissues that do not have normal innervation. While it is recognized that insensitive tissue increases the likelihood of ulceration and recurrence of ulceration, this review attempts to answer the question, Is wound healing impaired in denervated tissue? A review of the scientific literature of the past 35 years demonstrates that all phases of wound healing are impaired in denervated tissue, and these mechanisms are different from those related to one of the underlying diseases, diabetes. Understanding the value of innervation, a goal of wound healing should be to seek strategies that provide reinnervation to these at-risk tissues.

Neural Hedgehog signaling maintains stem cell renewal in the sensory touch dome epithelium

“…In lower vertebrates, intact nerves are required for blastema-mediated limb regeneration (30). Mammalian wound healing also is impaired by nerve loss (31,32); however, this impairment may be caused by patterning defects rather than stem cell dysregulation (33). In mice, autonomic innervation is critical for the proper establishment and maintenance of salivary gland stem cells during development (34).…”

313 Influence of the Neural Microenvironment in Prostate Cancer

“…Nerves are necessary in wounding re-epithelialization, which is impaired following denervation. 11,12 Furthermore, during development, the formation of the mouse pelvic floor is regulated by the androgendependent survival of a neuronal nucleus in the lower spinal cord. 1 Therefore, the effects of nerves on epithelial cells are not exclusive to cancer, as demonstrated by our data.…”

“…[3][4][5][6][7][8][9][10] Nerve-regulated functions are also important for wound repair and tissue homeostasis. [11][12][13] Nerves in the prostate peak in young adulthood, and then decrease with age. [14][15][16] Nerves and blood vessels co-evolve developmentally and are important components of the tumor microenvironment, along with carcinoma-associated stromal cells, matrix factors, and immune components.…”

A brief history of the study of nerve dependent regeneration

“…19 For further review of the role of nerves during mammalian wound healing, see ref. 20 Elucidating the underlying mechanisms of nerve dependency thus has wide-ranging implications for the study of human health and medicine.…”