Endogenous substance P production in the Achilles tendon increases with loading in an in vivo model of tendinopathy-peptidergic elevation preceding tendinosis-like tissue changes

J Musculoskelet Neuronal Interact. 2011 Jun;11(2):133-40.


Objectives: To quantify the intratendinous levels of substance P (SP) at different stages of overload in an established model for Achilles tendinopathy (rabbit). Also, to study the distribution of the SP-receptor, the NK-1R, and the source of SP, in the tendon.

Methods: Animals were subjected to the overuse protocol for 1, 3 or 6 weeks. One additional group served as unexercised controls. Immunoassay (EIA), immunohistochemistry (IHC), and in situ hybridisation (ISH) were performed.

Results: EIA revealed increased SP-levels in the Achilles tendon of the exercised limb in all the experimental groups as compared to in the controls (statistically significant; p=0.01). A similar trend in the unexercised Achilles tendon was observed but was not statistically significant (p=0.14). IHC and in ISH illustrated reactions of both SP and NK-1R mainly in blood vessel walls, but the receptor was also found on tenocytes.

Conclusions: Achilles tendon SP-levels are elevated already after 1 week of loading. This shows that increased SP-production precedes tendinosis, as tendinosis-like changes occur only after a minimum of 3 weeks of exercise, as shown in a recent study using this model. We propose that central neuronal mechanism may be involved as similar trends were observed in the contralateral Achilles tendon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Achilles Tendon / blood supply
  • Achilles Tendon / metabolism*
  • Achilles Tendon / physiopathology*
  • Animals
  • Disease Models, Animal
  • Female
  • Neuropeptides / biosynthesis*
  • Neuropeptides / physiology
  • Rabbits
  • Stress, Mechanical*
  • Substance P / biosynthesis*
  • Substance P / physiology
  • Tendinopathy / metabolism*
  • Tendinopathy / physiopathology*
  • Up-Regulation / physiology*
  • Weight-Bearing / physiology


  • Neuropeptides
  • Substance P