Resolving an inflammatory concept: the importance of inflammation and resolution in tendinopathy

Abstract

Injuries to the superficial digital flexor tendon (SDFT) are an important cause of morbidity and mortality in equine athletes, but the healing response is poorly understood. One important drive for the healing of connective tissues is the inflammatory cascade, but the role of inflammation in tendinopathy has been contentious in the literature. This article reviews the processes involved in the healing of tendon injuries in natural disease and experimental models. The importance of inflammatory processes known to be active in tendon disease is discussed with particular focus on recent findings related specifically to the horse. Whilst inflammation is necessary for debridement after injury, persistent inflammation is thought to drive fibrosis, a perceived adverse consequence of tendon healing. Therefore the ability to resolve inflammation by the resident cell populations in tendons at an appropriate time would be crucial for successful outcome. This review summarises new evidence for the importance of resolution of inflammation after tendon injury. Given that many anti-inflammatory drugs suppress both inflammatory and resolving components of the inflammatory response, prolonged use of these drugs may be contraindicated as a therapeutic approach. We propose that these findings have profound implications not only for current treatment strategies but also for the possibility of developing novel therapeutic approaches involving modulation of the inflammatory process.

Keywords: Inflammation; Injury; Pathogenesis; Resolution; Tendinopathy; Tendon.

Fig. 1

Schematic to propose the relationship between inflammation and resolution in the development of tendon injury. (A) In early stage injury, inflammation triggers a tendon resolution response, which appears to be transient and reduces with age and time after injury. During the later stages of healing (chronic injury) we propose that insufficient or dysregulated resolution allows low-level inflammation to persist, increasing the propensity for fibrotic healing and re-injury. (B) To improve the healing response of tendon, a potential therapeutic strategy is to moderate inflammation whilst simultaneously enhancing the tendons resolution response.