Journal
JOURNAL OF COMPARATIVE NEUROLOGY
Volume 507, Issue 3, Pages 1277-1299Publisher
WILEY
DOI: 10.1002/cne.21607
Keywords
CGRP-receptor; RAMP1; trigeminal ganglion; spinal trigeminal nucleus; headache
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Funding
- NIDDK NIH HHS [DK52388, DK39957, T32-DK07573, DK57840] Funding Source: Medline
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Calcitonin gene-related peptide (CGRP) is a key mediator in primary headaches including migraine., Animal models of meningeal nociception demonstrate both peripheral and central CGRP effects; however, the target structures remain unclear. To study the distribution of CGRP receptors in the rat trigeminovascular system we used antibodies recognizing two components of the CGRP receptor, the calcitonin receptor-like receptor (CLR) and the receptor activity-modifying protein 1 (RAMP1). In the cranial dura mater, CLR and RAMP1 immunoreactivity (-ir) was found within arterial blood vessels, mononuclear cells, and Schwann cells, but not sensory axons. In the trigeminal ganglion, besides Schwann and satellite cells, CLR- and RAMP1-ir was found in subpopulations of CGRP-ir neurons where colocalization of CGRP- and RAMP1-ir was very rare (approximate to 0.6%). CLR- and RAMP1-ir was present on central, but not peripheral, axons. In the spinal trigeminal nucleus, CLR- and RAMPI-ir was localized to glomerular structures, partly colocalized with CGRP-ir. However, CLR- and RAMP1-ir was lacking in central glia and neuronal cell bodies. We conclude that CGRP receptors are associated with structural targets of known CGRP effects (vasodilation, mast cell degranulation) and targets of unknown function (Schwann cells). In the spinal trigeminal nucleus, CGRP receptors are probably located on neuronal processes, including primary afferent endings, suggesting involvement in presynaptic regulation of nociceptive transmission. Thus, in the trigeminovascular system CGRP receptor localization suggests multiple targets for CGRP in the pathogenesis of primary headaches.
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