Article Text

other Versions

Substance P accelerates hypercellularity and angiogenesis in tendon tissue and enhances paratendinitis in response to Achilles tendon overuse in a tendinopathy model
  1. Gustav Andersson1,
  2. Ludvig J Backman1,
  3. Alexander Scott2,3,
  4. Ronny Lorentzon4,
  5. Sture Forsgren1,
  6. Patrik Danielson1
  1. 1Department of Integrative Medical Biology, Anatomy Section, Umeå University, Umeå, Sweden
  2. 2Department of Physical Therapy, University of British Columbia, Vancouver, British Columbia, Canada
  3. 3Centre for Hip Health and Mobility, Vancouver Coastal Health and Research Institute, Vancouver, British Columbia, Canada
  4. 4Department of Surgical and Perioperative Sciences, Sports Medicine Unit, Umeå University, Umeå, Sweden
  1. Correspondence to Dr Patrik Danielson, Department of Integrative Medical Biology, Anatomy Section, Umeå University, SE-901 87 Umeå, Sweden; patrik.danielson{at}


Background Tenocytes produce substance P (SP), and its receptor (neurokinin-1 receptor (NK-1R)) is expressed throughout the tendon tissue, especially in patients with tendinopathy and tissue changes (tendinosis) including hypercellularity and vascular proliferation. Considering the known effects of SP, one might ask whether SP contributes to these changes.

Objectives To test whether development of tendinosis-like changes (hypercellularity and angiogenesis) is accelerated during a 1-week course of exercise with local administration of SP in an established Achilles tendinopathy model.

Methods Rabbits were subjected to a protocol of Achilles tendon overuse for 1 week, in conjunction with SP injections in the paratenon. Exercised control animals received NaCl injections or no injections, and unexercised, uninjected controls were also used. Tenocyte number and vascular density, as well as paratendinous inflammation, were evaluated. Immunohistochemistry and in situ hybridisation to detect NK-1R were conducted.

Results There was a significant increase in tenocyte number in the SP-injected and NaCl-injected groups compared with both unexercised and exercised, uninjected controls. Tendon blood vessels increased in number in the SP-injected group compared with unexercised controls, a finding not seen in NaCl-injected controls or in uninjected, exercised animals. Paratendinous inflammation was more pronounced in the SP-injected group than in the NaCl controls. NK-1R was detected in blood vessel walls, nerves, inflammatory cells and tenocytes.

Conclusions SP accelerated the development of tendinosis-like changes in the rabbit Achilles tendon, which supports theories of a potential role of SP in tendinosis development; a fact of clinical interest since SP effects can be effectively blocked. The angiogenic response to SP injections seems related to paratendinitis.

Statistics from


  • Funding Financial support has been obtained from the Faculty of Medicine at Umeå University (SF, PD), the Sigurd and Elsa Golje Memorial Foundation (PD), the Tore Nilsson Foundation for Medical Research (PD), the J C Kempe and Seth M Kempe Memorial Foundations, Örnsköldsvik (SF) and Worksafe, British Columbia, Canada (AS).

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.