title: Temporal effects of topical morphine application on cutaneous wound healing.
abstract: BACKGROUND
  Studies have shown that topical administration of exogenous opioid drugs impairs wound healing by inhibiting the peripheral release of neuropeptides, thereby inhibiting neurogenic inflammation. This delay is immediate and peaks during the first days of wound closure. This study examined the effects of topical morphine treatment in a cutaneous wound healing model in the rat.
  
  
  METHODS
  Full-thickness 4-mm-diameter wounds were placed on the periscapular region of rats that subsequently received twice-daily topical applications of IntraSite Gel (Smith+Nephew, Hull, United Kingdom) alone or gel infused with 5 mm morphine sulfate on days 0-3 or 4-10 postwounding or throughout the time course. Wound tissue was taken on days 1, 3, 5, 8, and 18 postwounding and immunostained for myofibroblast and macrophage markers or stained with hematoxylin and eosin.
  
  
  RESULTS
  Delays in wound closure observed during morphine application on days 0-3 postwounding mimicked those seen in wounds treated with morphine throughout the entire healing process. However, no significant delays in closure were seen in wounds treated with morphine beginning on day 4 postwounding. Treatment of wounds with morphine significantly reduced the number of myofibroblasts and macrophages in the closing wound. In addition, morphine application resulted in decreases in skin thickness and an increase in residual scar tissue in healed skin.
  
  
  CONCLUSIONS
  These findings demonstrate the time-dependent and persistent nature of the detrimental effects of topical morphine on cutaneous wound healing. The data identify specific limitations that could be ameliorated to optimize topical opioid administration as an analgesic therapeutic strategy in the treatment of painful cutaneous wounds.
authors.affiliation: Department of Pharmacology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
authors.forename: Jerri M
authors.initials: JM
authors.lastname: Rook
authors.forename: Wohaib
authors.initials: W
authors.lastname: Hasan
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: McCarson
mesh_terms: D000287:Administration, Topical; D000818:Animals; D008297:Male; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology; D014949:Wounds, Nonpenetrating / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D009020:Morphine