A role for calcitonin gene-related peptide in rabbit knee joint ligament healing

Abstract

Knee joint ligament healing has been shown to be improved when the torn ligament ends remain in contact, however, the rationale for these effects is unknown. The sensory neuropeptide calcitonin gene related peptide (CGRP) has potent trophic and vasodilatatory properties and as such is thought to be advantageous in wound repair. In ascertaining a role for CGRP in rabbit medial collateral ligament healing, the present study examined changes in CGRP-like immunoreactivity (CGRP-LI) and CGRP-mediated vasomotor responses in gap injured (non-contact), Z-plasty apposed (contact), and sham operated control medial collateral ligaments. At 6 weeks post-trauma, CGRP-LI decreased in the healing zone of gap injured and Z-plasty apposed medial collateral ligaments compared with controls, and non-contact ligament nerve fibres exhibited an abnormal morphology. Topical administration of CGRP (10(-13) to 10(-9) mol) caused a dose-dependent increase in ligament perfusion in each experimental group of knees. The CGRP-mediated vasodilatation associated with gap injured ligaments was not significantly different from controls (P = 0.06), whereas apposed medial collateral ligaments showed an augmented response to the peptide (P < 0.0005). These findings indicate that the beneficial effects of ligament interposition post-trauma may be related to an enhanced responsiveness to CGRP in conjunction with a more typical re-innervation profile. Conversely, the aberrant characteristics of CGRP-LI nerves occurring in gap injured tissue is suggestive of impaired CGRP release which may explain the poor functional recovery associated with these ligaments.