Figure 2. Wound angiogenesis under the influence of opioids.
Topically applied opioids (left panel) increase VEGF receptor expression and stimulate PDGF receptors in wound-associated endothelial cells. Activation of PDGF receptors might result from PDGF, which is released from opioid-stimulated keratinocytes. Fentanyl augments NO concentration in wounds, which triggers VEGF synthesis in keratinocytes. Released VEGF may activate angiogenic signaling of up-regulated VEGF receptors in wound-associated endothelial cells. In contrast, systemic morphine prevents wound vascularization by hindering macrophages from wound infiltration and recruitment of endothelial progenitor cells (right panel).