Pain mediators and wound healing--establishing the connection.

Pain accompanies every disruption of the skin surface in a normal sensate individual. The intensity and duration of the pain varies depending on the nature of trauma, the healing trajectory and various host factors. Pain mediator release is the mechanism for pain perception following peripheral stimulus and central interpretation. The various mediators may have promoting effects on wound healing in the short term, but it appears that protracted release of these mediators may well have detrimental effects on wound healing. The exaggerated release of pain mediators may result in nociceptor hypersensitization, hyperinflammatory cellular and extracellular matrix (ECM) changes, and in some cases, the potential for a fibrotic healing pattern. This relates to an imbalance between mediators with differing healing characteristics arising in certain pathological conditions. In this respect, it may be worth examining pain mediator agonists or antagonists, not only on compassionate grounds of pain control, but relating to the potential effects on overall wound healing.