The etiology and pathogenesis of chronic tendon pain are unknown. Even though tendon biopsies having shown an absence of inflammatory cell infiltration, anti-inflammatory agents (non-steroidal anti-inflammatory drugs, corticosteroidal injections) are commonly used. We have demonstrated that it is possible to use intratendinous microdialysis to investigate human tendons, and found normal prostaglandin E2 (PGE2) levels in chronic painful tendinosis (Achilles and patellar) tendons. Furthermore, gene technological analyses of biopsies showed no upregulation of pro-inflammatory cytokines. These findings show that there is no PGE2-mediated intratendinous inflammation in the chronic stage of these conditions. The neurotransmitter glutamate (a potent modulator of pain in the central nervous system) was, for the first time, found in human tendons. Microdialysis showed significantly higher glutamate levels in chronic painful tendinosis (Achilles and patellar) tendons, compared with pain-free normal control tendons. The importance of this finding is under evaluation. Treatment is considered to be difficult, and not seldom, surgery is needed. However, recent researches on non-surgical methods have shown promising clinical results. Painful eccentric calf-muscle training has been demonstrated to give good clinical short- and mid-term results on patients with chronic painful mid-portion Achilles tendinosis. Good clinical results were associated with decreased tendon thickness and a structurally more normal tendon with no remaining neovessels. Using ultrasonography (US)+color Doppler (CD), and immunhistochemical analyses of biopsies, we have recently demonstrated a vasculo/neural (Substance-P and Calcitonin Gene-Related Peptide nerves) ingrowth in the chronic painful tendinosis tendon, but not in the pain-free normal tendon. A specially designed treatment, using US- and CD-guided injections of the sclerosing agent Polidocanol, targeting the neovessels outside the tendon, has been shown to cure tendon pain in pilot studies, in a majority of the patients. A recent, randomized, double-blind study verified the importance of injecting the sclerosing substance Polidocanol.