Chronic musculo-tendinous pain syndromes are relatively common and associated with very high socio-economic costs. Their aetiology and pathogenesis are still unknown. In the athletic population, chronic tendon pain is most often seen among recreational male and female athletes in the age group between 30-60 years, and is considered to be associated with overuse of the aged tendon. Treatment is known to be difficult. In general, these chronic painful conditions have been considered to include an inflammatory component, and the nomenclature used (tendinitis, tendonitis) most often implies an inflammatory involvement. Despite that tendon biopsies have shown an absence of inflammatory cell infiltration, anti-inflammatory agents (NSAID'S, corticosteroidal injections) are most often included in the treatment. Our research has been focused on chronic painful conditions in the Achilles-, patellar-, and extensor carpi radialis brevis (ECRB)-tendons. We have demonstrated, for the first time, that it is possible to use the microdialysis technique for in vivo investigations of human tendons, and that the excitatory neurotransmitter glutamate exists in human tendons. We have identified and measured the concentrations of prostaglandin E2 (PGE2) in tendons as well. The results showed that chronic painful tendinosis (Achilles-, patellar-, ECRB-) had significantly higher concentrations of glutamate, but not PGE2, as compared to the pain-free normal tendons. With the use of immunohistochemical analyses and enzyme histochemistry of human Achilles- and patellar tendon biopsies, we have also, for the first time demonstrated that glutamate NMDARI-immunoreaction was present in nerve structures. These findings altogether, indicate that glutamate might be involved in chronic tendon pain, and further emphasizes that there is no chemical inflammation (normal PGE2 levels) in the chronic stage of these relatively common so-called tendinopathies. The findings of glutamate and it's NMDARI-receptors might have implications for treatment and be a potential target for drugs.