title: Substance P accelerates hypercellularity and angiogenesis in tendon tissue and enhances paratendinitis in response to Achilles tendon overuse in a tendinopathy model.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Integrative Medical Biology, Anatomy Section, Umeå University, Sweden.
authors.forename: Gustav
authors.initials: G
authors.lastname: Andersson
authors.forename: Ludvig J
authors.initials: LJ
authors.lastname: Backman
authors.forename: Alexander
authors.initials: A
authors.lastname: Scott
authors.forename: Ronny
authors.initials: R
authors.lastname: Lorentzon
authors.forename: Sture
authors.initials: S
authors.lastname: Forsgren
authors.forename: Patrik
authors.initials: P
authors.lastname: Danielson
mesh_terms: D000125:Achilles Tendon / Q000098:blood supply*; D000279:Administration, Cutaneous; D000818:Animals; D049109:Cell Proliferation; D012090:Cumulative Trauma Disorders / Q000473:pathology*; D005260:Female; D009389:Neovascularization, Pathologic / Q000139:chemically induced; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000009:adverse effects*; D010805:Physical Conditioning, Animal / Q000009:adverse effects*; D011817:Rabbits; D011897:Random Allocation; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D013373:Substance P / Q000008:administration & dosage / Q000009:adverse effects*; D052256:Tendinopathy / Q000139:chemically induced* / Q000473:pathology
chemical_list: D018377:Neurotransmitter Agents; D018040:Receptors, Neurokinin-1; D013373:Substance P