Calcitonin‐gene‐related‐peptide‐immunoreactive innervation of the rat head with emphasis on specialized sensory structures

Abstract

The distribution of calcitonin-gene-related peptide-like immunoreactivity (CGRP-IR) was studied in sections of decalcified rat head and selected whole-mount preparations in order to address the complex peptidergic innervation patterns in peripheral cephalic specialized zones and to examine neuronal ganglia in situ. Labeled neuron somata in trigeminal, glossopharyngeal, and vagal ganglia comprised a large proportion of small to medium size type B ganglion cells. Parasympathetic ganglia (ciliary, otic, sphenopalatine, submandibular) revealed a small population of labeled somata and numerous perisomatic IR axons, whereas sympathetic ganglion cells (superior cervical) were devoid of label though richly innervated by perisomatic IR axons. The gustatory geniculate ganglion contained only a few labeled neurons and axons. Coarse peripheral CGRP-IR axons were traced to skeletal muscle motor end plates (e.g., lingual, tensor tympani, etc.), and thin sensory axons most densely innervated the cornea, iris, general integument, all mucosal epithelia lining the tympanic, nasal, sinus and oropharyngeal cavities, and the cerebral meninges. Blood vessels, glands, ducts, and their orifices were often heavily innervated, and specific specializations and exceptions are discussed. Distinctive patterns of IR innervation characterized the various specialized sensory systems, including (1) cochlear and vestibular hair cells; (2) lingual, palatal, oropharyngeal, and laryngoepiglottal taste buds; (3) main olfactory epithelium and axons projecting to glomeruli in specific sectors of main olfactory bulb; (4) septal-olfactory organ; (5) vomeronasal organ; and (6) the nervus terminalis system. Secretory epithelia (ciliary body, choroid plexus, and stria vascularis) were notably lacking in CGRP-IR. Despite the multiplicity of functionally distinct CGRP neuronal and axonal populations, certain generalizations merit consideration. The extensive innervation of chemosensory nasal and oral epithelia may contribute to specific chemical sensitivities (e.g., relating to olfactory and gustatory senses) as well as evoking “nociceptive” responses to chemical irritants as part of a “common chemical sense.” An efferent role for some of these peptidergic afferent axons may also be inferred from their specific distributions. Sites involved in regulating access to and sensitivity of sense organs to external stimuli (e.g., cochlear and vestibular hair cells, taste bud orifices, and main olfactory epithelium) are heavily innervated. Other IR axons are in position to exert control over airflow through nasal turbinates, glandular secretion, blood circulation, and duct transport systems. The widespread distribution of “free” nerve endings in ocular, nasal, and oral epithelia may serve versatile roles in response to noxious chemical stimuli, permitting “sensory” axon modulation of autonomic neuron activity and triggering of protective reflexes. Direct peptidergic axon effector control of stimulus-evoked processes including secretion (e.g., salivation), bronchoconstriction, the ocular injury response, and generalized withdrawal from aversive stimuli might also be mediated by sensory CGRP-IR axons.