NGF and TrkA receptor expression in chronic tendon ruptures: potential role in the pathogenesis of degenerative tendon lesions

Aim of our study was to investigate the expression of nerve growth factor (NGF) and its tyrosine kinase receptor (TrkA) on tendinosic tissue harvested from Achilles and rotator cuff tendons. The presence of NGF and TrkA receptor was proven through immunofluorescence. We randomly recruited 6 patients that underwent rotator cuff arthroscopic repair and 10 patients that were treated for an acute Achilles tendon lesion. During surgery we harvested samples of the rotator cuff and of Achilles tendon. Furthermore we took a sample of macroscopically healthy tissue from each Achilles tendon. Fromeach specimen 4 slideswere obtained.Two slideswere employed for the search of NGF, one was treated with specific antibodies and marked with FITC (Fluorescein Isothiocyanate Conjugated), the second slide was for control purposes and was exposed to FITC, butwithout prior exposition to the specific antibody.The same procedurewas repeated to obtain on two more slides in order to repeat the search for Trka, with specific antibodies. All the slides were studied on a fluoromicroscope. The analysis of these specimens revealed the presence of the NGF and of the TrkA in all the rotator cuff specimens: the immunoistochemical reaction between the specimens and the specific antibodies marked with FITC was seen under fluoromicroscopy, but in none of the control cases treated with only FITC. The samples of Achilles tendon revealed the presence of NGF in 9 of 10 cases. In one case the sample was negative for NGF and TrkA receptor and no inflammatory reaction was spotted. The specimens harvested from the macroscopically healthy Achilles tendon revealed no inflammatory reaction and immunofluorescence revealed no NGF or TrkA receptor expression. There is considerable evidence that shows that the system constituted by the NGF and his high-affinity receptor TrkA plays a fundamental role in the molecular processes underlying the main forms of persistent pain.This indicates a possible therapeutic area for the antibodies that could block the NGF/TrkA system, in order to modulate the frequency and the duration of the action potential of nociceptive neurons during chronic inflammation. NGF and TrkA were absent on normal tissue and increased on degenerative tendon specimens. These findings could suggest a role of NGF in the pathophysiology of degenerative tendon rupture.