This investigation describes, to our knowledge, the first experiment where the microdialysis technique was used to study certain metabolic events in human patellar tendons in combination with immunohistochemical analyses of tendon biopsies. In five patients (four men and one woman) with a long duration (range 12-36 months) of pain symptoms from Jumper's knee (localized tenderness in the patellar tendon verified as tendon changes with ultrasonography or MRI), and in five controls (four men and one woman) with normal patellar tendons, a standard microdialysis catheter was inserted into the patellar tendon under local anestesia. The local concentrations of glutamate (excitatory neurotransmitter) and prostaglandin Ez (PGE?) were registered under resting conditions. Samplings were done every 15 min during a 2 h period. In all individuals (patients and controls) biopsies were taken for immunohistochemical analyses.The results showed that it was possible to detect and measure the concentrations of glutamate and PGE2 in the patellar tendon with the use of microdialysis technique. There were significantly higher concentrations of free glutamate, but not PGE?, in tendons with tendinosis compared to normal tendons. In the biopsies, there were no inllammatory cell infiltrates, but, for the first time, it was shown that there was immunoreaction for the glutamate receptor NMDARl in association with nerve structures in human patellar tendons. These findings altogether indicate that glutamate might be involved in painful Jumper's knee, and further emphasizes that there is no chemical inflammation (normal PGEz levels) in this chronic condition. 0 2001 Elsevier Science Ltd. All rights reserved. IntroductionThe aetiology and pathogenesis to Jumper's knee is unknown [4,13]. This condition is most often seen among athletes engaged in high loading sports, and microtearing of the collagen fibers in the patellar tendon has been proposed as a possible causative factor [13]. It is known that when a tendon is stretched to more than 5% of elongation there is a risk of tendon microfailures to occur [ll]. During sport activities such as jumping (landing phase 8 kN) and weight-lifting (17 times body weight) very high forces may be reached in the patellar tendon impose stresses high enough to cause fiber failure [15]. However, it needs to be emphasized that the etiology, patogenesis, and pain mechanisms associated with this condition are not clearly understood.The tendon pathology has been characterized to be related to abnormal collagen, ground substance, tenocytes, and vasculature [12,13]. The presence of inflammation in this condition has been debated, nevertheless, the absence of inflammatory cells in biopsies, in clinical praxis, this group of patients is often treated with antiinflammatory agents (NSAIDs, local corticosteroidal injections) [ 12,131. Microdialysis has been shown to be a useful technique to investigate certain metabolic events in different types of human tissue [5,18]. Microdialysis allows continuous measurements...

This investigation was to our knowledge the first to use the microdialysis technique to study concentrations of substances in a human tendon. In four patients (mean age 40.7 years) with a painful nodule in the Achilles tendon (chronic Achilles tendinosis) and in five controls (mean age 37.2 years) with normal Achilles tendons (confirmed by ultrasonography) the local concentrations of glutamate and prostaglandin E2 were measured under resting conditions. A standard microdialysis catheter was inserted into the Achilles tendon under local anesthesia. Sampling was performed every 15 min over a 4-h period. The results showed significantly higher concentrations of glutamate in tendons with tendinosis than in normal tendons (196 +/- 59 vs. 48 +/- 27 mumol/l, P < 0.05), and there were no significant changes in glutamate concentration over the period of investigation. There were no significant differences in the mean concentrations of prostaglandin E2 (83 +/- 22 vs. 54 +/- 24 pg/ml) between tendons with tendinosis and normal tendons. In conclusion, in situ microdialysis appears a useful method to study certain metabolic events in tendon tissue. The higher concentrations of the excitatory neurotransmitter glutamate in Achilles tendons with a painful nodule may possibly be involved in the pain mechanism in this chronic condition. Furthermore, there were no signs of inflammation in the tendons with painful nodules, as indicated by the normal prostaglandin E2 levels.

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In this investigation, we show the presence of both free glutamate (microdialysis) and glutamate NMDAR1 receptors (immunohistochemical analyses of tendon biopsies), in tendons from patients with chronic Achilles tendon pain (Achilles tendinosis) and in controls (pain-free tendons). The NMDAR1 immunoreaction was usually confined to acetylcholinesterase-positive structures, implying that the reaction is present in nerves. Glutamate is a potent pain mediator in the human central nervous system, and in animals it has been shown that peripherally administered glutamate NMDA receptor antagonists diminish the response to formalin-induced nociception. Our present finding of glutamate NMDA receptors in human Achilles tendons might have implications for pain treatment.