Naltrexone Accelerates Full‐Thickness Cutaneous Wound Healing by Enhancing Remodeling (Abstract)

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Naltrexone Accelerates Full‐Thickness Cutaneous Wound Healing by Enhancing Remodeling

The FASEB Journal
01 April 2013

Patients with Type 1 diabetes (T1D) risk complications from impaired wound healing, and the pathophysiology of wound repair is poorly understood. Delayed repair of full‐thickness cutaneous wounds in T1D rats is reversed by blockade of the opioid growth factor receptor (OGFr) with topically applied naltrexone (NTX), an opioid antagonist. NTX accelerates wound closure and angiogenesis of cutaneous wounds in both T1D and normal rats. To evaluate wound remodeling, streptozotocin‐induced T1D rats, and normal rats, with 6 mm cutaneous wounds, were topically treated with NTX or sterile saline in moisturizing cream (3x/day) for 20 days. Tissue specimens were evaluated for tensile strength, matrix metalloproteinase‐9 (MMP‐9) expression and collagen maturation. Collagen maturation, as measured by Sirius red staining, revealed that T1D NTX‐treated wounds showed a 45‐fold increase in maturation compared to T1D controls after 20 days of treatment. On day 20, T1D controls had significantly less MMP‐9 expression within the wound compared to T1D NTX‐treated and normal rats. By day 60 post‐wounding, tensile strength values of wounds in T1D rats treated with NTX were comparable to those in normal rats, whereas vehicle treated T1D wounds displayed significantly lower tensile strengths. In summary, blockade of endogenous opioids by NTX provided a non‐toxic biological treatment that accelerated wound remodeling in T1D rats.