The pathogenesis of Achilles tendinopathy: A systematic review

The Achilles Tendinopathy: Pathogenesis Review

“…Neovascularization with thick walls, a tortuous appearance and small lumen ventral from the Achilles tendon and in the paratenon is found in 50-88% of symptomatic tendons but not in pain-free tendons [128,129] ; these blood vessels are accompanied by sensory neonerves [130,131] causing an increase in pain signaling by producing nociceptive substances such as glutamate, substance P, calcitonin gene-related peptide (CGRP) past the critical threshold [132,133] . Myofibroblasts proliferate and are transported by the new blood vessels into the peritendineum and the tendon proper [16,30] . Myofibroblasts synthesise abundant amount of collagen to repair the tendon causing also the formation of scar tissue around the tendon: consequently adhesions of the paratenon onto the Achilles tendon can be found at the location of the neurovascular ingrowth.…”

“…Intratendinous changes can be caused by intrinsic or extrinsic factors, the combination of which is responsible for chronic tendinopathy onset and development [30] .…”

“…In addiction, such neuropeptides (substance P, acetylcholine, catecholamines and glutamate) seems to be related to the bilateral nature of changes seen in Achilles tendinopathy; many patients present with bilateral Achilles tendinosis [107] and many of those initially presenting unilateral symptoms develop contralateral ones over time [108] . It has been demonstrated in the rat that unilateral training leads to bilateral changes in levels of neuropeptides in the synovial fluids [109,110] ; on the basis of these and other observation has recently been formulated the hypothesis of the "central neuronal Bondi M et al Achilles tendinopathy mechanism" as a possible explanation for the frequent bilateral involvement in Achilles tendinopathy [30,111] .…”

“…Deepening the mechanisms with which ischemia could damage tendons, it has been demonstrated that when a tendon is under maximal tensile load, ischemia occurs [29] , and then, upon relaxation, reperfusion occurs, generating oxygen free radicals [73] that may result in damage to the tendon. However, recently was demonstrated a correlation between hypoxia and VEGF production: in vitro studies with isolated tenocytes from rat Achilles tendons have shown that hypoxia is an important inducer of VEGF expression [30,63] . In order to understand what this correlation between hypoxia and VEGF increasing consists in, it must be firstly remembered that oxygen tension plays a key role in regulating the expression of various genes; among them there is, for example, the well-known erythropoietin (Epo) gene: low oxygen tension stimulates Epogene expression to increase new red cells production.…”

“…Although short periods at 45℃ are unlikely to result in tenocyte death, repeated hyperthermic insults and prolonged durations of exposure may compromise cell viability and produce tendon degeneration [55,56] . Systemic Diseases: Many systemic diseases are associated with general defects in matrix metabolism and structure that compromise tendon strength and elasticity or result in inflammation of the tendon or its insertion [27,30,[57][58][59][60] . These conditions must be considered as part of the differential diagnosis.…”