Opioid Antagonists Enhance Diabetic Wound Closure: A New Therapy

Abstract

A major complication of type 1 or type 2 diabetes involves proper healing of cutaneous wounds. Diabetic wounds heal slowly and treatments do not mediate the underlying pathophysiology. Enkephalins are reported to be elevated in diabetes and one enkephalin, opioid growth factor (OGF), serves as an inhibitory growth factor that delays cell replication. OGF interacts with its receptor, OGFr, to mediate cellular homeostasis, including wound repair. Blockade of the inhibitory function of OGF using the antagonist naltrexone (NTX) accelerates cell proliferation in a receptormediated, non-toxic manner. Topical application of NTX to full-thickness cutaneous wounds in type 1 diabetic rats and type 2 diabetic mice accelerated three phases of wound closure that are normally [defective, retarded] in diabetes including initial re-epithelialization, new blood vessel formation, and establishment of granulation tissue and integrity of the skin. These data support observations that a novel biological pathway is impaired under diabetic conditions and can be corrected by topical NTX to accelerate diabetic wound healing.