Glutamate receptors in tendinopathic patients

J Orthop Res. 2012 Sep;30(9):1447-52. doi: 10.1002/jor.22094. Epub 2012 Feb 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Humans
  • Male
  • Nerve Tissue Proteins / metabolism*
  • Patellar Ligament / metabolism*
  • Phosphorylation
  • Receptors, Metabotropic Glutamate / metabolism*
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Substance P / metabolism*
  • Tendinopathy / metabolism*
  • Young Adult


  • GRIN1 protein, human
  • Nerve Tissue Proteins
  • Receptors, Metabotropic Glutamate
  • Receptors, N-Methyl-D-Aspartate
  • Substance P