The Yin and Yang of the Opioid Growth Regulatory System: Focus on Diabetes—The Lorenz E. Zimmerman Tribute Lecture

Figure 18

Effect of NTX treatment on wound healing rate of standardized skin wounds. Left: the impact of daily or three times daily NTX in moisturizing cream (MCN) on the healing rate of standard cutaneous wounds. Left (a): untreated diabetic rats had skin wounds that were 24%, 44%, and 132% greater than those of normal animals on days 5, 7, and 9, respectively, after wounding. Left (b, upper): within three days of a single or three times daily regimen of 10⁻⁵ M NTX in MCN, the wounded areas of normal rats were reduced by 30% and 11%, on the respective days, compared to other normal animals receiving MCN + vehicle. Left (b, lower): diabetic (DB) animals subjected to once daily application of MCN + NTX had a decreased wound size compared with DB rats exposed to vehicle, but the greatest effect was achieved with MCN + NTX given three times daily, which consistently accelerated wound closure, resulting in mean residual wounds that were reduced by 13% to 57% from DB rats treated with MCN + vehicle. Values represent means ± SEM. Significantly different from normal or MCN + vehicle at , , and . Right: histology of skin comparing normal and DB rats receiving vehicle or NTX. The overall appearance is similar, without evidence of necrosis, and so forth. Nevertheless, epithelial thickness in normal rats ( μm) was 44% greater than in DB rats receiving vehicle. Normal animals treated with NTX, as well as DB rats subjected to NTX, did not differ in the thickness of the epithelium relative to normal animals receiving vehicle (derived from [64]).