Autonomic nerve dysfunction and impaired diabetic wound healing: The role of neuropeptides

Abstract

Lower extremity ulcerations represent a major complication in diabetes mellitus and involve multiple physiological factors that lead to impairment of wound healing. Neuropeptides are neuromodulators implicated in various processes including diabetic wound healing. Diabetes causes autonomic and small sensory nerve fibers neuropathy as well as inflammatory dysregulation, which manifest with decreased neuropeptide expression and a disproportion in pro- and anti- inflammatory cytokine response. Therefore to fully understand the contribution of autonomic nerve dysfunction in diabetic wound healing it is crucial to explore the implication of neuropeptides. Here, we will discuss recent studies elucidating the role of specific neuropeptides in wound healing.

Figure 1. Diabetic neuropathy and neuropeptide dysregulation contribute to lower extremity wound pathogenesis

Diabetes mellitus causes autonomic and small sensory nerve fibers neuropathy in the lower extremity as well as inflammatory dysregulation, which manifest with reduced neuropeptide expression and disproportion in pro- and anti- inflammatory cytokine response. Neuropeptides have a direct effect on leukocytes and further contribute to the cytokine imbalance. Also, cytokines and neuropeptides directly influence various skin cells including fibroblasts, keratinocytes and endothelial cells decreasing their proliferation and resulting in irregular angiogenesis, ECM production and reepithelialization. Reduced neovascularization, reepithelialization and dysregulation in remodeling and granulation tissue deposition, also affected by the abnormal cytokine expression profile, lead to impaired cutaneous wound healing. Adapted from (9).