Nonsteroidal anti-inflammatory drugs for wounds: pain relief or excessive scar formation?

Abstract

The inflammatory process has direct effects on normal and abnormal wound healing. Hypertrophic scar formation is an aberrant form of wound healing and is an indication of an exaggerated function of fibroblasts and excess accumulation of extracellular matrix during wound healing. Two cytokines--transforming growth factor-beta (TGF-beta) and prostaglandin E2 (PGE2)--are lipid mediators of inflammation involving wound healing. Overproduction of TGF-beta and suppression of PGE2 are found in excessive wound scarring compared with normal wound healing. Nonsteroidal anti-inflammatory drugs (NSAIDs) or their selective cyclooxygenase-2 (COX-2) inhibitors are frequently used as a pain-killer. However, both NSAIDs and COX-2 inhibitors inhibit PGE2 production, which might exacerbate excessive scar formation, especially when used during the later proliferative phase. Therefore, a balance between cytokines and medication in the pathogenesis of wound healing is needed. This report is a literature review pertaining to wound healing and is focused on TGF-beta and PGE2.

Figure 1

Wound healing of fetal skin with little scarring. Very little inflammatory reaction occurs in fetal skin, which results in little scarring and nearly perfect recovery of fetal skin. Several environment and intrinsic factors are believed to play a role in this process.

Figure 2

Normal process of wound healing. The initial inflammatory phase begins at the time of wounding, when the activation of the coagulation cascade causes the release of cytokines that stimulate chemotaxis of neutrophils and macrophages into the wound to begin early debridement (1). The proliferative phase is signified by an abundance of fibroblasts and an accumulation of extracellular matrix (ECM) (2). The abundant ECM is then degraded and the immature type III collagen of the early wound is modified into mature type I collagen in final remodeling, or mature phase. A good healing process involves several enhancement factors.

Figure 3

The hypertrophic scarring healing result. A hypertrophic scar possesses several surface characteristics that distinguish it from normal scar formation. There are several initiating factors participate the process. Due to a slow and prolonged regression phase, excessive type III collagens excreted from fibroblasts are accumulated in a direction parallel to epidermal surface. The evolution of myofibroblast from fibroblast may cause wound retraction in the future.

Figure 4

The keloid healing result. Several surface characteristics of keloid mark its difference from hypertrophic scar. However, there is only one difference in the initiating factors. There is no remolding phase in this aberrant wound healing process, and fibroblasts will not eventually turn into myofibroblasts. The abnormal scar is composed of disorganized type I and III collagens with thick irregular branched septa. On the cut surface, tongue-like advancing edges provoke its local advanced infiltrating nature.