The Anti-Calcitonin Gene-Related Peptide (Anti-CGRP) Antibody Fremanezumab Reduces Trigeminal Neurons Immunoreactive to CGRP and CGRP Receptor Components in Rats

Vogler B, Kuhn A, Mackenzie KD, Stratton J, Dux M, Meßlinger K (2023)

Publication Type: Journal article

Publication year: 2023

Journal

International Journal of Molecular Sciences MDPI

Book Volume: 24

Article Number: 13471

Journal Issue: 17

DOI: 10.3390/ijms241713471

Abstract

Treatment with the anti-CGRP antibody fremanezumab is successful in the prevention of chronic and frequent episodic migraine. In preclinical rat experiments, fremanezumab has been shown to reduce calcitonin gene-related peptide (CGRP) release from trigeminal tissues and aversive behaviour to noxious facial stimuli, which are characteristic pathophysiological changes accompanying severe primary headaches. To further decipher the effects of fremanezumab that underlie these antinociceptive effects in rats, immunohistochemistry and ELISA techniques were used to analyse the content and concentration of CGRP in the trigeminal ganglion, as well as the ratio of trigeminal ganglion neurons which are immunoreactive to CGRP and CGRP receptor components, 1–10 days after subcutaneous injection of fremanezumab (30 mg/kg) compared to an isotype control antibody. After fremanezumab treatment, the fraction of trigeminal ganglion neurons which were immunoreactive to CGRP and the CGRP receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) was significantly lowered compared to the control. The content and concentration of CGRP in trigeminal ganglia were not significantly changed. A long-lasting reduction in CGRP receptors expressed in trigeminal afferents may contribute to the attenuation of CGRP signalling and antinociceptive effects of monoclonal anti-CGRP antibodies in rats.

Authors with CRIS profile

Birgit Vogler Lehrstuhl für Physiologie Annette Kuhn Lehrstuhl für Physiologie Karl Meßlinger Professur für Zelluläre und Molekulare Neurophysiologie

Involved external institutions

Teva Pharmaceutical Industries Ltd. IL Israel (IL) University of Szeged / József Attila Tudományegyetem Szeged HU Hungary (HU)

How to cite

APA:

Vogler, B., Kuhn, A., Mackenzie, K.D., Stratton, J., Dux, M., & Meßlinger, K. (2023). The Anti-Calcitonin Gene-Related Peptide (Anti-CGRP) Antibody Fremanezumab Reduces Trigeminal Neurons Immunoreactive to CGRP and CGRP Receptor Components in Rats. International Journal of Molecular Sciences, 24(17). https://doi.org/10.3390/ijms241713471

MLA:

Vogler, Birgit, et al. "The Anti-Calcitonin Gene-Related Peptide (Anti-CGRP) Antibody Fremanezumab Reduces Trigeminal Neurons Immunoreactive to CGRP and CGRP Receptor Components in Rats." International Journal of Molecular Sciences 24.17 (2023).

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