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 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
International journal of molecular sciences - 24(2023), 17 vom: 30. Aug. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Vogler, Birgit [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.09.2023 Date Revised 11.09.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms241713471 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Vogler, Birgit |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The Anti-Calcitonin Gene-Related Peptide (Anti-CGRP) Antibody Fremanezumab Reduces Trigeminal Neurons Immunoreactive to CGRP and CGRP Receptor Components in Rats |
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| 500 | |a Date Revised 11.09.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CGRP release | |
| 650 | 4 | |a calcitonin gene-related peptide | |
| 650 | 4 | |a fremanezumab | |
| 650 | 4 | |a migraine pain | |
| 650 | 4 | |a monoclonal antibody | |
| 650 | 4 | |a rat | |
| 650 | 4 | |a trigeminal ganglion | |
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| 650 | 7 | |a fremanezumab |2 NLM | |
| 650 | 7 | |a Receptors, Calcitonin Gene-Related Peptide |2 NLM | |
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| 700 | 1 | |a Kuhn, Annette |e verfasserin |4 aut | |
| 700 | 1 | |a Mackenzie, Kimberly D |e verfasserin |4 aut | |
| 700 | 1 | |a Stratton, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Dux, Mária |e verfasserin |4 aut | |
| 700 | 1 | |a Messlinger, Karl |e verfasserin |4 aut | |
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