A novel mutation in glial fibrillary acidic protein gene in a patient with Alexander disease

Previous studies in our laboratory have shown that the neuropeptide, calcitonin gene-related peptide (CGRP) accumulates at a site of inferior alveolar nerve injury at the time when high levels of spontaneous activity and mechanical sensitivity are recorded electrophysiologically. The present study was undertaken to determine whether or not the CGRP could be playing a role in initiating or modulating the neuronal activity. In 18 anaesthetised adult ferrets the left inferior alveolar nerve was sectioned and ligated and recovery permitted for 3 days. Under a second anaesthetic recordings were made 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 CGRP antagonist (CGRP 8-37) were applied either by close-arterial injection or topically (10(-4) M, 0.2 ml). After each application activity was recorded for a 30 min period. Recordings were made from 52 units, of which 26 (50%) were spontaneously active and 30 (58%) were mechanically sensitive. The spontaneous activity in five units was increased by the application of CGRP, and the CGRP antagonist subsequently reduced the activity in two of these units. Activity was induced by CGRP in three previously silent units. Overall, activity was affected in 19% of the units studied. We conclude that CGRP present within a neuroma may initiate or modulate the level of ectopic discharge from some damaged nerve fibres and therefore may contribute to the sensory disturbances which follow nerve injury.