title: Plasticity of peptidergic innervation in healing rabbit medial collateral ligament.
abstract: BACKGROUND
  Denervation substantially impairs healing of the medial collateral ligament (MCL). Because normal ligaments are sparsely innervated, we hypothesized that neuropeptide-containing neurons would sprout or proliferate after ligament transection, followed by later regression with healing, in a manner analogous to blood vessels.
  
  
  METHODS
  We transected the right MCL in 9 mature female New Zealand white rabbits and killed 3 rabbits at 2, 6 or 14 weeks. Alternate sets of 12-mm serial sections of healing MCL scars were examined by fluorescent immunohistochemistry for substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY) and pan-neuronal marker PGP9.5.
  
  
  RESULTS
  Normal MCLs had few peptidergic fibres located in the epiligament in a perivascular pattern. At 2 weeks, PGP9.5-, SP-and CGRP-positive fibres had increased in the epiligament adjacent to the injury. By 6 weeks, there were increases in CGRP-and PGP9.5-positive fibres in epiligament and scar, with similar but less marked increases in SP-positive fibres. At 14 weeks, there was notable regression of immunostained peptidergic nerve fibres in the scar.
  
  
  CONCLUSIONS
  This experiment shows evidence for a remarkable plasticity of ligament innervation after injury, supporting the idea that neuronal factors play a fundamental role in wound healing.
authors.affiliation: McCaig Institute for Bone and Joint Health, Department of Surgery, University of Calgary, Calgary, Alta. salo@ucalgary.ca
authors.forename: Paul T
authors.initials: PT
authors.lastname: Salo
authors.forename: Jasmine A
authors.initials: JA
authors.lastname: Beye
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Seerattan
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Leonard
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Ivie
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bray
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D017888:Medial Collateral Ligament, Knee / Q000293:injuries* / Q000294:innervation* / Q000378:metabolism; D009473:Neuronal Plasticity; D009478:Neuropeptide Y / Q000378:metabolism; D011817:Rabbits; D013373:Substance P / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D009478:Neuropeptide Y; D013373:Substance P; D043222:Ubiquitin Thiolesterase; D015740:Calcitonin Gene-Related Peptide