Expert Reviews in Molecular Medicine

Review Article

Inflammation and neuropeptides: the connection in diabetic wound healing

Leena Pradhana1, Christoph Nabzdyka2, Nicholas D. Andersena1, Frank W. LoGerfoa1 and Aristidis Vevesa3 c1

a1 Department of Surgery, Division of Vascular Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

a2 Charité University Medicine, Joined Medical Faculty of Free University and Humboldt University, Berlin, Germany.

a3 Department of Surgery, Microcirculation Laboratory, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Abstract

Abnormal wound healing is a major complication of both type 1 and type 2 diabetes, with nonhealing foot ulcerations leading in the worst cases to lower-limb amputation. Wound healing requires the integration of complex cellular and molecular events in successive phases of inflammation, cell proliferation, cell migration, angiogenesis and re-epithelialisation. A link between wound healing and the nervous system is clinically apparent as peripheral neuropathy is reported in 30–50% of diabetic patients and is the most common and sensitive predictor of foot ulceration. Indeed, a bidirectional connection between the nervous and the immune systems and its role in wound repair has emerged as one of the focal features of the wound-healing dogma. This review provides a broad overview of the mediators of this connection, which include neuropeptides and cytokines released from nerve fibres, immune cells and cutaneous cells. In-depth understanding of the signalling pathways in the neuroimmune axis in diabetic wound healing is vital to the development of successful wound-healing therapies.

Correspondence

c1 Corresponding author: Aristidis Veves, Microcirculation Laboratory, Beth Israel Deaconess Medical Center, Palmer 317, West Campus, One Deaconess Rd, Boston, MA 02215, USA. Tel: +1 617 632 7075; Fax: +1 617 632 0860; E-mail: aveves@bidmc.harvard.edu