Fig. 4. Effects of topical morphine on skin architecture of fully closed cutaneous wounds. Rats were treated with IntraSite Gel (Smith+Nephew, Hull, United Kingdom) alone or gel infused with 5 mm morphine sulfate (MS) twice daily through wound day 18. (  A ) Epidermal thickness of new skin in wounds. Note that topical morphine treatment resulted in significantly thinner epidermis than that in control wounds. (  B ) Full thickness of the new skin covering closed cutaneous wounds following topical morphine treatment. Similarly, the full skin thickness was diminished following topical morphine administration. (  C ) Area of scar tissue covering closed cutaneous wounds following topical morphine treatment. Scar tissue was defined as the visibly distinct new epithelium covering the original wound site. Scar size is presented as area (mm²) mean ± SEM, and was determined by analysis of digital images of closed wounds on day 18 after wounding. Treatment of the wounds with 5 mm morphine sulfate significantly increased the scar area compared with controls treated with gel only (n = 4–7). *  P < 0.05 comparison between morphine and controls treated with gel only (unpaired Student  t test).