Ribbans (2013) offers an excellent review of the genetic background of Achilles tendinopathy.
Puddu classified the pathological features (of mid-portion tendon pathology, although the term was not used at the time of Puddu's series) into:
- peritendonitis, with inflammation of the paratenon only
- peritendonitis with tendinosis, with inflammation of the paratenon and abnormalities of the tendon
- tendinosis, with abnormality of the tendon only
- rupture (acute rupture is dealt with separately)
The histopathology of Achilles tendonopathy is the same as other similar degenerative conditions, such as plantar fasciits, tibialis posterior tendonopathy, tennis elbow and rotator cuff degeneration
- Wavy collagen fibres with hyalinisation and fibre separation by increased ground substance
- Cell proliferation, marked variation in cellularity, with rounded cell nuclei
- Irregular neovascularisation
- Cystic spaces
Samples from patients with history of rupture rather than simple tendonopathy showed the same changes, but twice as severe. There is some evidence that patients who present with tendon pain and those who present with rupture are different populations (Tallon et al 2001, Jones 2006, Corps 2006). mRNA studies of matrix proteoglycans (Corps 2006) found that aggrecan and biglycan expression were increased markedly in tendonpathy, while the typical finding in ruptured tendons was reduced decorin expression. Studies of mRNA for matrix metalloproteases (important in tissue turnover) show these to be different in normal, tendonopathic and ruptured tendons (Alfredson 2003, Jones 2006). Variations in expression of these genes between individuals (Raleigh 2009, September 2009) indicate that injury or abnormal stress on the tendon may lead to altered matrix metabolism, neovascularisation and painful nerve ingrowth in genetically susceptible individuals
Pearce (2009) found increased markers of apoptosis and nitric acid synthesis in 14 cases of tendonopathy compared with control areas of the same tendons. There are no significant numbers of inflammatory cells - this is a degenerative condition with attempts at repair. Alfredson (1999, 2001, 2003) found no evidence of prostaglandin-mediated inflammatory processes using micro-dialysis and gene activation analyses. Inflammation of the paratendon does show some acute inflammatry cells, along with vascular engorgement.
So where does the pain come from? Various pain-mediating neurotransmitters, such as glutamate (Alfredson 1999) and substance P (Schubert 2005), have been described in tendonopathy, and these appear to be associated with the new vessel formation that is showns by colour Doppler and histological analysis (Schubert 2005, Bjur 2005). Lactate levels are higher in tendonopathy (Alfredson 2002).
Several studies have suggested neovascularisation(or particularly the nerves that accompany the neovessels) seem to be important in the causation of pain, and ablation of the neovessels relieves pain (Alfredson 2005, Lind 2006, Knobloch 2007, Richards 2009). The sites of maximum tenderness and neovascularisation are closely correlated (Divani 2010).
However, neovascularisation can be seen in normal tendons (de Vos 2007) and may persist despite treatment. de Jonge (2013) studied 127 patients with Achilles tendinopathy and found the Ohberg neovascularisation score and VISA-A score were only weakly correlated; indeed only the function sub-score of the VISA-A showed a significant correlation.
There is a paradox here. The blood supply of the Achilles tendon has been examined by various techniques:
- counting blood vessels on histology slides
- power Doppler examination
The current consensus is that there is a zone of hypovascularisation from 2-6cm above the insertion, although not all studies support this. This is the zone in which most tendonopathy and rupture occur, and it has been suggested that ischaemia is involved in the causation of tendonopathy, which might fit with the increased lactate levels (Alfredson 2002). Perhaps the neovascularisation, associated with pain-mediating nerve endings, is partly prompted by chronic or intermittent ischaemia.
As well as the degenerative changes in the tendon itself, insertional tendonopathy also shows (Rufai 1995):
- Bone spurs arising from the posteroinferior insertion
- Splits in the tendon, mostly longitudinal
- Degeneration of the fibrocartilage that lies on the deep surface of the tendon next to the retrocalcaneal bursa