title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Dept. of Integrative Medical Biology, Anatomy, Umea University, Umea, Sweden.
authors.forename: L J
authors.initials: LJ
authors.lastname: Backman
authors.forename: G
authors.initials: G
authors.lastname: Andersson
authors.forename: G
authors.initials: G
authors.lastname: Wennstig
authors.forename: S
authors.initials: S
authors.lastname: Forsgren
authors.forename: P
authors.initials: P
authors.lastname: Danielson
mesh_terms: D000125:Achilles Tendon / Q000098:blood supply / Q000378:metabolism* / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D009479:Neuropeptides / Q000096:biosynthesis* / Q000502:physiology; D011817:Rabbits; D013314:Stress, Mechanical; D013373:Substance P / Q000096:biosynthesis* / Q000502:physiology; D052256:Tendinopathy / Q000378:metabolism* / Q000503:physiopathology*; D015854:Up-Regulation / Q000502:physiology*; D016474:Weight-Bearing / Q000502:physiology
chemical_list: D009479:Neuropeptides; D013373:Substance P