ArticleThe journal of headache and pain2024
Anti-CGRP antibody galcanezumab modifies the function of the trigeminovascular nocisensor complex in the rat.
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 6 papers.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- A delayed endothelial-glial mechanism for CGRP-induced migraine.The journal of headache and pain · 2026Review
- Functional characterisation of dura mater αCGRP degradation fragments at vascular, immune, and CGRP receptor targets.The journal of headache and pain · 2026Article
- Review
- Histamine plasma levels from dietary histidine/histamine intake correlate with CGRP in trigeminal tissues.The journal of headache and pain · 2025Article
- Substance P release from rat dura mater is inversely correlated with CGRP release- experiments using glycerol trinitrate and anti-CGRP antibodies.The journal of headache and pain · 2025Article
- Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMonoclonal antibodies directed against the neuropeptide calcitonin gene-related peptide (CGRP) are effective in the prevention of chronic and frequent episodic migraine. Since the antibodies do not cross the blood brain barrier, their antinociceptive effect is attributed to effects in meningeal tissues. We aimed to probe if such an antibody can be visualized within the dura mater and the trigeminal ganglia following its administration to rats and to examine if the activity of the trigeminovascular nocisensor complex is influenced by this treatment.
methodsEffects of the anti-CGRP antibody galcanezumab on the trigeminovascular nocisensor complex was examined by measuring release of sensory neuropeptides and histamine from the rat dura mater. Deposits of galcanezumab were visualized by fluorescence microscopy in the trigeminal ganglion and the dura mater.
resultsFluorophore-labelled galcanezumab was detected in the dura mater and the trigeminal ganglion up to 30 days after treatment affirming the long-lasting modulatory effect of this antibody. In female rats, seven days after systemic treatment with galcanezumab the capsaicin-induced release of CGRP was decreased, while that of substance P (SP) was increased in the dura mater. In control rats, release of the inhibitory neuropeptide somatostatin (SOM) was higher in females than in males. Stimulation with high concentration of KCl did not significantly change the release of SOM in control animals, while in rats treated with galcanezumab SOM release was slightly reduced. Galcanezumab treatment also reduced the amount of histamine released from dural mast cells upon stimulation with CGRP, while the effect of compound 48/80 on histamine release was not changed.
conclusionsGalcanezumab treatment is followed by multiple changes in the release of neuropeptides and histamine in the trigeminal nocisensor complex, which may contribute to the migraine preventing effect of anti-CGRP antibodies. These changes affecting the communication between the components of the trigeminal nocisensor complex may reduce pain susceptibility in migraine patients treated with CGRP targeting monoclonal antibodies.
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