Normal development and effects of neonatal infraorbital nerve damage upon the innervation of the trigeminal brainstem complex by primary afferent fibers containing calcitonin gene‐related peptide

Abstract

Immunocytochemistry was used to study the normal development and response to infraorbital nerve (ION) damage of the innervation of the trigeminal (V) brainstem complex by axons recognized by an antibody directed against calcitonin gene-related peptide (CGRP). CGRP-like immunoreactivity (CGRPLI) was present in axons that occupied the outer V spinal tract (TrV) at all levels of the V brainstem complex. Almost no fibers terminated within V nucleus principalis (PrV), but there was dense CGRPLI in the supratrigeminal nucleus. There was also very little CGRPLI within rostral V subnucleus oralis (SpO). However, in the caudal one-half of the nucleus, a dense elongated patch of immunoreactivity was consistently present just medial to TrV. Only occasional CGRP-positive axons could be seen within V subnucleus interpolaris (SpI), but the paratrigeminal nucleus contained dense immunoreactivity. Trigeminal subnucleus caudalis (SpC) also contained CGRPLI that was very dense in lamina I and the outer portion of lamina II. Scattered terminals were also present in layers III and IV and dense terminal clusters were in lamina V. CGRP-immunoreactive neurons were present in the V ganglion by embryonic (E-) day 16 and immunoreactive axons could be seen in the V brainstem complex on E-17. At birth, CGRP-positive axons in the V brainstem complex had achieved a distribution very similar to that in adult rats. The major difference between the patterns of labelling in neonates and adults was the presence of relatively large numbers of CGRP-positive fibers in ventral PrV and SpO of the former animals. The disappearance of these fibers was completed by the middle of the third postnatal week. Transection of the ION on the day of birth had little effect upon CGRP in SpO, SpI, and SpC, but it did result in an increase in CGRP-positive fibers in PrV ipsilateral to the damaged nerve. When considered together with previous findings, these results suggest that CGRP-positive axons express this peptide well after they have entered the V brainstem complex and that the central terminal field of these fibers is not substantially altered by a manipulation which results in the death of nearly 60% of all V primary afferent neurons.