Calcitonin gene-related peptide- and substance P-containing primary afferent fibers in the dorsal column of the rat

Abstract

The dorsal column and its nuclei exhibit a considerable number of fibers containing neuropeptides, such as calcitonin gene-related peptide (CGRP) and substance P (SP), whose origins and functional roles are as yet unknown. The present study attempts to determine the origin and nature of these fibers by means of immunohistochemistry combined with several experimental manipulations. A similar study was done on scattered substance P (SP) fibers whose presence was confirmed in this study. Transection of the upper cervical cord of rats resulted in an accumulation of CGRP, sometimes with SP also, in the caudal aspect of the lesion, thus indicating the presence of peptide-containing ascending fibers. Hemitransection of the dorsal column at the level of C 2–3 caused reduction of CGRP-containing fibers in the dorsal column and its nuclei on the operated side. Electron microscopic observation of the nucleus gracilis revealed that CGRP-like immunoreactive terminals made direct axodendritic synaptic contacts. Medium- to large-sized neurons in the dorsal root ganglia were labeled with Fast blue dye which was injected into the dorsal column nuclei. These included medium- to large-sized neurons exhibiting immunoreactivity to CGRP-like substances, and neurons of a medium size which were immunoreactive to SP-like compounds. The incidence of the former was higher at the thoracic level than at the cervical and lumbar levels, while that of the latter was very low. Electron microscopic observation of CGRP-containing fibers in the cervical region of the dorsal column revealed that 88% of these fibers were unmyelinated and the remainder were thinly myelinated. These results indicate that medium- to large-sized CGRP- (and SP)-containing neurons in the dorsal root ganglia give rise to fine fibers into the dorsal column and may terminate in the dorsal column nuclei.