Glutamate receptors in tendinopathic patients

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 (r² = 0.54, p = 0.03), but not in the controls (r² = 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. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1447–1452, 2012