0810 - Nerve Regeneration - a Prerequisite for Tendon Healing?

INTRODUCTION Research on the mechanisms regulating tendon healing has predominantly focused on mechanical rather than biological features. Over the last decade, however, accumulating data suggests that besides cytokines and vascular factors also neuronal mediators are critical components of tissue repair. A variety of neuronal mediators, so called neuropeptides, have been identified and found to exert nociceptive, vasoactive, inflammatory and, notably, also trophic effects in several tissues. As for tendons, however, not even the normal innervation has been clarified. This applies not only to the type of nerve fibres, but also to the specific transmitters. Recently, we were able to demonstrate the sensory neuropeptides substance P and calcitonin gene related peptide (CGRP) in normal rat Achilles tendon [1]. Considering that neuropeptides have been shown to mediate trophic effects, it is quite plausible that an intact nervous system is a prerequisite for normal tendon healing. This, however, presupposes a potent and rapid nerve regenerative capability after rupture. To our knowledge, this issue has not been addressed previously in studies of tendon healing. It may prove that nerve regeneration including a complete renewal of transmitters is required for normal neovascularisation or/and the proliferation/differentiation of different cell types involved in tissue repair. In the present study, the occurrence of nerve fibres during healing of ruptured Achilles tendon was monitored up to 8 weeks post rupture. A specific marker of nerve regeneration, the B-50/growth associated protein 43 (GAP), and a marker for mature nerve fibres, the protein gene product 9.5 (PGP), were used. An attempt was also made to quantify these two neuronal markers over time. Moreover, the occurrence of two specific transmitters representing the sensory and autonomic nervous system was analysed, i.e. CGRP and neuropeptide Y (NPY).