The Anti-Calcitonin Gene-Related Peptide (Anti-CGRP) Antibody Fremanezumab Reduces Trigeminal Neurons Immunoreactive to CGRP and CGRP Receptor Components in Rats
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...
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/17/13471 |
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| author | Birgit Vogler Annette Kuhn Kimberly D. Mackenzie Jennifer Stratton Mária Dux Karl Messlinger |
| author_facet | Birgit Vogler Annette Kuhn Kimberly D. Mackenzie Jennifer Stratton Mária Dux Karl Messlinger |
| author_sort | Birgit Vogler |
| collection | DOAJ |
| description | 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. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:21:42Z |
| publishDate | 2023-08-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a1ea3b8bf19d4d70ba4a1c5aa148042f2023-11-19T08:17:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124171347110.3390/ijms241713471The Anti-Calcitonin Gene-Related Peptide (Anti-CGRP) Antibody Fremanezumab Reduces Trigeminal Neurons Immunoreactive to CGRP and CGRP Receptor Components in RatsBirgit Vogler0Annette Kuhn1Kimberly D. Mackenzie2Jennifer Stratton3Mária Dux4Karl Messlinger5Institute of Physiology and Pathophysiology, Friedrich-Alexander-University, D-91054 Erlangen, GermanyInstitute of Physiology and Pathophysiology, Friedrich-Alexander-University, D-91054 Erlangen, GermanyTeva Pharmaceuticals, Redwood City, CA 94063, USATeva Pharmaceuticals, Redwood City, CA 94063, USADepartment of Physiology, University of Szeged, H-6720 Szeged, HungaryInstitute of Physiology and Pathophysiology, Friedrich-Alexander-University, D-91054 Erlangen, GermanyTreatment 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.https://www.mdpi.com/1422-0067/24/17/13471fremanezumabmonoclonal antibodycalcitonin gene-related peptidetrigeminal ganglionCGRP releaserat |
| spellingShingle | Birgit Vogler Annette Kuhn Kimberly D. Mackenzie Jennifer Stratton Mária Dux Karl Messlinger 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 fremanezumab monoclonal antibody calcitonin gene-related peptide trigeminal ganglion CGRP release rat |
| title | The Anti-Calcitonin Gene-Related Peptide (Anti-CGRP) Antibody Fremanezumab Reduces Trigeminal Neurons Immunoreactive to CGRP and CGRP Receptor Components in Rats |
| title_full | The Anti-Calcitonin Gene-Related Peptide (Anti-CGRP) Antibody Fremanezumab Reduces Trigeminal Neurons Immunoreactive to CGRP and CGRP Receptor Components in Rats |
| title_fullStr | The Anti-Calcitonin Gene-Related Peptide (Anti-CGRP) Antibody Fremanezumab Reduces Trigeminal Neurons Immunoreactive to CGRP and CGRP Receptor Components in Rats |
| title_full_unstemmed | The Anti-Calcitonin Gene-Related Peptide (Anti-CGRP) Antibody Fremanezumab Reduces Trigeminal Neurons Immunoreactive to CGRP and CGRP Receptor Components in Rats |
| title_short | The Anti-Calcitonin Gene-Related Peptide (Anti-CGRP) Antibody Fremanezumab Reduces Trigeminal Neurons Immunoreactive to CGRP and CGRP Receptor Components in Rats |
| title_sort | anti calcitonin gene related peptide anti cgrp antibody fremanezumab reduces trigeminal neurons immunoreactive to cgrp and cgrp receptor components in rats |
| topic | fremanezumab monoclonal antibody calcitonin gene-related peptide trigeminal ganglion CGRP release rat |
| url | https://www.mdpi.com/1422-0067/24/17/13471 |
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