Calcitonin gene-related peptide modifies the ectopic discharge from damaged nerve fibres in the ferret

Previous studies in our laboratory have shown that the neuropeptide, calcit onin gene-related peptide (CGRP) accumulates at a site of inferior alveolar nerve injury at the time when high levels of spontaneous activity and mech anical sensitivity are recorded electrophysiologically. The present study w as undertaken to determine whether or not the CGRP could be playing a role in initiating or modulating the neuronal activity. In 18 anaesthetised adul t ferrets the left inferior alveolar nerve was sectioned and ligated and re covery permitted for 3 days. Under a second anaesthetic recordings were mad e from a fine nerve filament, containing up to four active or silent units, dissected from the nerve proximal to the injury. After recording activity for a 30 min control period, CGRP and then the CORP antagonist (CGRP 8-37) were applied either by close-arterial injection or topically (10(-4) M, 0.2 mi). After each application activity was recorded for a 30 min period. Rec ordings were made from 52 units, of which 26 (50%) were spontaneously activ e and 30 (58%) were mechanically sensitive. The spontaneous activity in fiv e units was increased by the application of CG RP, and the CORP antagonist subsequently reduced the activity in two of these units. Activity was induc ed by CORP in three previously silent units. Overall, activity was affected in 19% of the units studied. We conclude that CGRP present within a neurom a may initiate or modulate the level of ectopic discharge from some damaged nerve fibres and therefore may contribute to the sensory disturbances whic h follow nerve injury. (C) 2001 Elsevier Science Ireland Ltd. All rights re served.