Plasticity of peptidergic innervation in healing rabbit medial collateral ligament.
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.
Salo
Paul T
PT
McCaig Institute for Bone and Joint Health, Department of Surgery, University of Calgary, Calgary, Alta. salo@ucalgary.ca
Beye
Jasmine A
JA
Seerattan
Ruth A
RA
Leonard
Catherine A
CA
Ivie
Tyler J
TJ
Bray
Robert C
RC
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*
D009478:Neuropeptide Y; D013373:Substance P; D043222:Ubiquitin Thiolesterase; D015740:Calcitonin Gene-Related Peptide