ArticleThe journal of headache and pain2024
Sex differences in expression of CGRP family of receptors and ligands in the rat trigeminal system.
Article in The journal of headache and pain, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Sex-specific management of migraine a systematic review and consensus statement from the European Headache Federation (EHF).The journal of headache and pain · 2026Pooled it
- The cerebrospinal fluid-contacting nucleus CGRP-RAMP1-PKA signaling pathway mediates trigeminal neuralgia and its mechanism.The Korean journal of pain · 2026Article
- Mechanisms of Acupuncture on the Neurovascular Unit in Migraine: A Narrative Review.European journal of neurology · 2026Review
- A delayed endothelial-glial mechanism for CGRP-induced migraine.The journal of headache and pain · 2026Review
- Cochlear Functional Changes and CGRP Modulation in a Chronic Nitroglycerin Migraine-Like Rat Model.The European journal of neuroscience · 2026Article
- Identifying cardiac safety signals of disproportionate reporting for CGRP antagonists: evidence from the FDA Adverse Event Reporting System.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Non-neuronal targets for migraine therapy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Trends and age-period-cohort analysis of migraine incidence in China from 1990 to 2021.PloS one · 2026Article
- Optogenetic cortical spreading depression originating from the primary visual cortex induces migraine-like pain and anxiety behaviors in freely moving C57BL/6 J mice.The journal of headache and pain · 2025Article
- Sex differences in the effects of calcitonin gene-related peptide signaling on migraine-like behavior in animal models: a narrative review.Frontiers in neurology · 2025Review
- Integrated pan-cancer analysis of ADM's role in prognosis, immune modulation and resistance.Frontiers in immunology · 2025Article
- Sex differences in the expression of calcitonin gene-related peptide (CGRP) and its receptor: a review of contradictory and nuanced findings.Neurobiology of pain (Cambridge, Mass.)Review
- Article
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Funding
Abstract
backgroundCalcitonin gene-related peptide (CGRP) is part of the calcitonin peptide family, which includes calcitonin (CT), amylin (AMY), and adrenomedullin (ADM). CGRP and its receptor are highly present in the trigeminovascular system (TVS). Recent research suggests that other members of the calcitonin family could be feasible therapeutic targets in the treatment of migraine. The present study aims to elucidate the distribution of ADM, AMY, CT, and their receptors in the rat TVS, and to explore potential sex differences in their expression.
methodsTrigeminal ganglia (TG) were dissected from male and female adult rats. Protein and gene expression were assessed through immunohistochemistry and RT-qPCR. Additionally, the dura mater was isolated for further investigation of protein expression and fiber localization using immunohistochemistry.
resultsQuantitative gene expression analysis revealed the presence of all genes in male and female TGs, except for calcitonin receptor (CTR). Notably, CGRP mRNA levels in TG were several folds higher than those of other genes. The receptor activity-modifying protein-1 (RAMP1) mRNA levels were significantly higher in female compared to male. No AMY or CT immunoreactivity was observed in the TVS. In contrast, immunoreactivity for ADM, CGRP, RAMP1, CTR, and calcitonin-like receptor (CLR) were observed in the cytoplasm of TG neurons. Immunoreactive Aδ-fibers storing RAMP1, ADM and CLR were also identified. RAMP2 and RAMP3 were expressed in nucleus of TG neurons and in satellite glial cells. Furthermore, RAMP1 and CLR were co-localized with CASPR in the nodes of Ranvier located in Aδ-fibers.
conclusionsThis study provides valuable insights into the distribution of the CGRP family of peptides and their receptors in the TVS. CGRP mRNA levels in the TG were markedly higher than those of other genes, demonstrating the key role of CGRP. The co-localization of CLR and RAMP1 on Aδ-fibers with CASPR suggests a potential role for this receptor in modulating trigeminal nerve function and neuronal excitability, with implications for migraine pathophysiology. Additionally, RAMP1 mRNA levels were significantly higher in female TG compared to males, indicating sex-specific differences in gene expression. These findings underscore the need for further research into the functional significance of gender-related variations.
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