ArticleNeurobiology of pain (Cambridge, Mass.)
Sex differences in the expression of calcitonin gene-related peptide receptor components in the spinal trigeminal nucleus.
Article in Neurobiology of pain (Cambridge, Mass.). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Cochlear Functional Changes and CGRP Modulation in a Chronic Nitroglycerin Migraine-Like Rat Model.The European journal of neuroscience · 2026Article
- CGRP receptor-expressing neurons in the central amygdala contributes to injury-induced pain hypersensitivity.bioRxiv : the preprint server for biology · 2026Article
- Migraine in men.The journal of headache and pain · 2025Review
- Female-selective mechanisms promoting migraine.The journal of headache and pain · 2024Review
- Calcitonin gene-related peptide: a possible biomarker in migraine patients with patent foramen ovale.BMC neurology · 2024Article
- CGRP physiology, pharmacology, and therapeutic targets: migraine and beyond.Physiological reviews · 2023Review
- Sex differences in pain along the neuraxis.Neuropharmacology · 2022Review
- B vitamins and their combination could reduce migraine headaches: A randomized double-blind controlled trial.Current journal of neurology · 2022Article
- A Female-Specific Role for Calcitonin Gene-Related Peptide (CGRP) in Rodent Pain Models.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Sex Differences in CGRP Regulation and Function in the Amygdala in a Rat Model of Neuropathic Pain.Frontiers in molecular neuroscience · 2022Article
- Lipidated Calcitonin Gene-Related Peptide (CGRP) Peptide Antagonists Retain CGRP Receptor Activity and Attenuate CGRP ActionFrontiers in pharmacology · 2022Article
- Inhibiting endocytosis in CGRPNature communications · 2021Article
- Effects of Calcitonin-Gene-Related-Peptide on Auditory Nerve Activity.Frontiers in cell and developmental biology · 2021Article
- Serum Calcitonin Gene-Related Peptide and Receptor Protein Levels in Patients With Fibromyalgia Syndrome: A Cross-Sectional Study.Archives of rheumatology · 2020Article
- Is There Any MRI Pattern That Discriminates Female From Male Migraine Patients?Frontiers in neurology · 2019Review
- 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
- Activating transcription factor 3 (ATF3) and calcitonin gene-related peptide (CGRP) increase in trigeminal ganglion neurons in female rats after photorefractive keratectomy (PRK)-like corneal abrasion.Neurobiology of pain (Cambridge, Mass.)Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
background and purposeCalcitonin gene-related peptide (CGRP) plays an important role in migraine pathophysiology. CGRP acts primarily by activating a receptor composed of 3 proteins: calcitonin receptor-like receptor (CLR), receptor activity-modifying protein 1 (RAMP1), and receptor component protein (RCP). We tested the hypothesis that sex differences exist in protein levels of two key components of this CGRP receptor: CLR and RCP.
methodsWe used specific antibodies to assess baseline protein levels of CLR and RCP in the spinal trigeminal nucleus caudalis (SpVc) and upper cervical spinal cord of both male and female rats. We also tested if manipulations that knock-down the expression of RCP in SpVc, using locally-mediated gene transfer of short hairpin RNA (shRNA), ameliorate pain in an animal model of intracranial migraine-like pain induced by chemical noxious stimulation of the meninges. To assess pain, we used tests of ongoing pain (rat face grimace test and freezing behavior) and tests of facial mechanical hypersensitivity and allodynia.
resultsThere was no difference in CLR levels between male and female animals (p > 0.11) in SpVc and the upper cervical cord. However, female animals exhibited greater baseline levels of RCP (up to 3-fold higher) compared to males (p < 0.002). The knock-down of RCP expression in SpVc attenuated mechanical facial allodynia induced by chemical noxious stimulation of the meninges, but had little effect on ongoing pain behaviors in female and male animals.
conclusionsRCP is an integral component of the CGRP receptor and may play a key role in mediating CGRP induced central sensitization after noxious stimulation of the meninges. RCP expression in the SpVc and upper cervical cord is sexually dimorphic, with higher levels of expression in females. This dimorphism may be related to the increased incidence of migraines in females-a hypothesis that should be tested in the future.
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