title: Glutamate receptors in tendinopathic patients.
abstract: Tendinopathy, pain, and degeneration, may be related to the up-regulation of substance P (SP) and its activation of glutamate receptors. We hypothesized that the pathogenesis of tendinopathy involves N-methyl-D-aspartate receptor type 1 (NMDAR1) activation (phosphorylated NMDAR1; phospho-NMDAR1) co-existing with SP. Moreover, we examined the presence of metabotropic receptors that increase (mGluR1 and mGluR5) or decrease (mGluR6 and mGluR7) NMDAR1 excitability. Biopsies from patients with patellar tendinopathy (n = 10) and from controls (n = 8) were immunohistochemically analyzed according to the occurrence and tissue distribution of NMDAR1, phosho-NMDAR1, mGluR (1, 5-7), and SP. The biopsies were immunohistochemically single- and double-stained and semi-quantitatively assessed. Tendinopathic biopsies exhibited increased occurrence of NMDAR1, phospho-NMDAR1, SP, and mGluR5, while mGluR6-7 were not increased and mGluR1 was not found. The occurrence of NMDAR1 and SP correlated in tendinopathy (r(2)  = 0.54, p = 0.03), but not in the controls (r(2)  = 0.11, p = 0.4). Co-localization of SP and phospho-NMDAR1 within the tendon proper was only found in tendinopathy, localized on hypertrophic tenocytes, blood vessels, and penetrating free-nerve fibres. Up-regulation and activation of the glutamate receptor, phospho-NMDAR1, suggests a role in the pathophysiology of tendinopathy. Increased NMDAR1 excitability may be related to increased SP and mGluR5. The unique co-existence of SP and phospho-NMDAR1 in tendinopathy presumably reflects a tissue proliferative and nociceptive role.
authors.affiliation: Orthopedic Laboratory, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nikos
authors.initials: N
authors.lastname: Schizas
authors.forename: Rudiger
authors.initials: R
authors.lastname: Weiss
authors.forename: Oystein
authors.initials: O
authors.lastname: Lian
authors.forename: Frede
authors.initials: F
authors.lastname: Frihagen
authors.forename: Roald
authors.initials: R
authors.lastname: Bahr
authors.forename: Paul W
authors.initials: PW
authors.lastname: Ackermann
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017847:Patellar Ligament / Q000378:metabolism*; D010766:Phosphorylation; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D052256:Tendinopathy / Q000378:metabolism*; D055815:Young Adult
chemical_list: C485668:GRIN1 protein, human; D009419:Nerve Tissue Proteins; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D013373:Substance P