@article{MTMT:34783723,
	title = {Glycerol Trinitrate Acts Downstream of Calcitonin Gene-Related Peptide in Trigeminal Nociception—Evidence from Rodent Experiments with Anti-CGRP Antibody Fremanezumab},
	url = {https://m2.mtmt.hu/api/publication/34783723},
	author = {Benedicter, Nicola and Vogler, Birgit and Kuhn, Annette and Schramm, Jana and Mackenzie, Kimberly D. and Stratton, Jennifer and Dux, Mária and Messlinger, Karl},
	doi = {10.3390/cells13070572},
	journal-iso = {CELLS-BASEL},
	journal = {CELLS},
	volume = {13},
	unique-id = {34783723},
	abstract = {Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) have been recognized as important mediators in migraine but their mechanisms of action and interaction have not been fully elucidated. Monoclonal anti-CGRP antibodies like fremanezumab are successful preventives of frequent migraine and can be used to study CGRP actions in preclinical experiments. Fremanezumab (30 mg/kg) or an isotype control monoclonal antibody was subcutaneously injected to Wistar rats of both sexes. One to several days later, glyceroltrinitrate (GTN, 5 mg/kg) mimicking nitric oxide (NO) was intraperitoneally injected, either once or for three consecutive days. The trigeminal ganglia were removed to determine the concentration of CGRP using an enzyme-linked immunosorbent assay (ELISA). In one series of experiments, the animals were trained to reach an attractive sugar solution, the access to which could be limited by mechanical or thermal barriers. Using a semi-automated registration system, the frequency of approaches to the source, the residence time at the source, and the consumed solution were registered. The results were compared with previous data of rats not treated with GTN. The CGRP concentration in the trigeminal ganglia was generally higher in male rats and tended to be increased in animals treated once with GTN, whereas the CGRP concentration decreased after repetitive GTN treatment. No significant difference in CGRP concentration was observed between animals having received fremanezumab or the control antibody. Animals treated with GTN generally spent less time at the source and consumed less sugar solution. Without barriers, there was no significant difference between animals having received fremanezumab or the control antibody. Under mechanical barrier conditions, all behavioral parameters tended to be reduced but animals that had received fremanezumab tended to be more active, partly compensating for the depressive effect of GTN. In conclusion, GTN treatment seems to increase the production of CGRP in the trigeminal ganglion independently of the antibodies applied, but repetitive GTN administration may deplete CGRP stores. GTN treatment generally tends to suppress the animals’ activity and increase facial sensitivity, which is partly compensated by fremanezumab through reduced CGRP signaling. If CGRP and NO signaling share the same pathway in sensitizing trigeminal afferents, GTN and NO may act downstream of CGRP to increase facial sensitivity.},
	year = {2024},
	eissn = {2073-4409},
	orcid-numbers = {Dux, Mária/0000-0002-9941-8188; Messlinger, Karl/0000-0002-8099-3860}
}

@article{MTMT:34521870,
	title = {Anti-CGRP antibody galcanezumab modifies the function of the trigeminovascular nocisensor complex in the rat},
	url = {https://m2.mtmt.hu/api/publication/34521870},
	author = {Friedrich, Nadine and Németh, Krisztina and Tanner, Martin and Rosta, Judit and Kisné Dobos, Ildikó and Oszlács, Orsolya and Jancsó, Gábor and Messlinger, Karl and Dux, Mária},
	doi = {10.1186/s10194-024-01717-2},
	journal-iso = {J HEADACHE PAIN},
	journal = {JOURNAL OF HEADACHE AND PAIN},
	volume = {25},
	unique-id = {34521870},
	issn = {1129-2369},
	abstract = {Background: Monoclonal 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. Methods: Effects 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. Results: Fluorophore-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. Conclusions: Galcanezumab 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. © 2024, The Author(s).},
	keywords = {Adult; Female; Male; HISTAMINE; NEUROPEPTIDE; immunohistochemistry; animal experiment; drug effect; sex difference; trigeminus ganglion; drug mechanism; monoclonal antibody; calcitonin gene related peptide; sensory nerve; substance P; Fluorescence microscopy; Arteriole; compound 48-80; systemic therapy; somatostatin release; Middle meningeal artery; galcanezumab; pain receptor; rat},
	year = {2024},
	eissn = {1129-2377},
	orcid-numbers = {Jancsó, Gábor/0000-0002-0496-3416; Dux, Mária/0000-0002-9941-8188}
}

@article{MTMT:34138634,
	title = {The Anti-Calcitonin Gene-Related Peptide (Anti-CGRP) Antibody Fremanezumab Reduces Trigeminal Neurons Immunoreactive to CGRP and CGRP Receptor Components in Rats},
	url = {https://m2.mtmt.hu/api/publication/34138634},
	author = {Vogler, Birgit and Kuhn, Annette and Mackenzie, Kimberly D. and Stratton, Jennifer and Dux, Mária and Messlinger, Karl},
	doi = {10.3390/ijms241713471},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {24},
	unique-id = {34138634},
	issn = {1661-6596},
	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.},
	year = {2023},
	eissn = {1422-0067},
	orcid-numbers = {Dux, Mária/0000-0002-9941-8188; Messlinger, Karl/0000-0002-8099-3860}
}

@article{MTMT:33916944,
	title = {Semi-Automated Recording of Facial Sensitivity in Rat Demonstrates Antinociceptive Effects of the Anti-CGRP Antibody Fremanezumab},
	url = {https://m2.mtmt.hu/api/publication/33916944},
	author = {Benedicter, Nicola and Messlinger, Karl and Vogler, Birgit and Mackenzie, Kimberly D. and Stratton, Jennifer and Friedrich, Nadine and Dux, Mária},
	doi = {10.3390/neurolint15020039},
	journal-iso = {NEUROL INT},
	journal = {NEUROLOGY INTERNATIONAL},
	volume = {15},
	unique-id = {33916944},
	issn = {2035-8385},
	abstract = {Migraine pain is frequently accompanied by cranial hyperalgesia and allodynia. Calcitonin gene-related peptide (CGRP) is implicated in migraine pathophysiology but its role in facial hypersensitivity is not entirely clear. In this study, we investigated if the anti-CGRP monoclonal antibody fremanezumab, which is therapeutically used in chronic and episodic migraines, can modify facial sensitivity recorded by a semi-automatic system. Rats of both sexes primed to drink from a sweet source had to pass a noxious mechanical or heat barrier to reach the source. Under these experimental conditions, animals of all groups tended to drink longer and more when they had received a subcutaneous injection of 30 mg/kg fremanezumab compared to control animals injected with an isotype control antibody 12–13 days prior to testing, but this was significant only for females. In conclusion, anti-CGRP antibody, fremanezumab, reduces facial sensitivity to noxious mechanical and thermal stimulation for more than one week, especially in female rats. Anti-CGRP antibodies may reduce not only headache but also cranial sensitivity in migraineurs.},
	year = {2023},
	eissn = {2035-8377},
	pages = {622-637},
	orcid-numbers = {Messlinger, Karl/0000-0002-8099-3860; Dux, Mária/0000-0002-9941-8188}
}

@article{MTMT:34185920,
	title = {Migrénben alkalmazott CGRP ellenes és CGRP receptor ellenes antitest kezelés trigeminális nociceptív funkciót módosító hatásának vizsgálata},
	url = {https://m2.mtmt.hu/api/publication/34185920},
	author = {Friedrich, Nadine and Tanner, Martin and Rosta, Judit and Németh, Krisztina and Dux, Mária},
	journal-iso = {FÁJDALOM : A MAGYARORSZÁGI FÁJDALOM TÁRSASÁG KIADVÁNYA},
	journal = {FÁJDALOM: A MAGYARORSZÁGI FÁJDALOM TÁRSASÁG KIADVÁNYA},
	volume = {2022},
	unique-id = {34185920},
	issn = {1789-8749},
	year = {2022},
	pages = {17-18},
	orcid-numbers = {Dux, Mária/0000-0002-9941-8188}
}

@article{MTMT:33287654,
	title = {A 2021. évi orvosi-élettani Nobel-díjjal elismert kutatások és azok magyar előzményei},
	url = {https://m2.mtmt.hu/api/publication/33287654},
	author = {Helyes, Zsuzsanna and Sántha, Péter and Pintér, Erika and Pethő, Gábor and Barthó, Loránd and Dux, Mária and Jancsó, Gábor},
	doi = {10.1556/2065.183.2022.6.6},
	journal-iso = {MAGYAR TUDOMÁNY},
	journal = {MAGYAR TUDOMÁNY},
	volume = {183},
	unique-id = {33287654},
	issn = {0025-0325},
	year = {2022},
	eissn = {1588-1245},
	pages = {738-751},
	orcid-numbers = {Sántha, Péter/0000-0003-0552-0358; Pintér, Erika/0000-0001-9898-632X; Dux, Mária/0000-0002-9941-8188; Jancsó, Gábor/0000-0002-0496-3416}
}

@misc{MTMT:33076370,
	title = {CGRP ellenes monoklonális antitestterápia hatásmechanizmusának vizsgálata állatmodellen},
	url = {https://m2.mtmt.hu/api/publication/33076370},
	author = {Friedrich, Nadine and Tanner, M and Rosta, Judit and Németh, K and Jancsó, Gábor and Dux, Mária},
	unique-id = {33076370},
	year = {2022},
	orcid-numbers = {Jancsó, Gábor/0000-0002-0496-3416; Dux, Mária/0000-0002-9941-8188}
}

@CONFERENCE{MTMT:33076329,
	title = {CGRP binding monoclonal antibodies modify trigeminal efferent functions},
	url = {https://m2.mtmt.hu/api/publication/33076329},
	author = {Dux, Mária},
	booktitle = {12th Congress of the European Pain Federation EFIC 2022-04-27 [Dublin, Írország]},
	unique-id = {33076329},
	year = {2022},
	pages = {EFIC 2022 Workshop},
	orcid-numbers = {Dux, Mária/0000-0002-9941-8188}
}

@CONFERENCE{MTMT:33076058,
	title = {Investigation of meningeal peptidergic sensory innervation following experimental subarachnoid hemorrhage},
	url = {https://m2.mtmt.hu/api/publication/33076058},
	author = {Masood, T and Karcsúné Kis, Gyöngyi and Algerafi, A and Lakatos, Szandra and Dux, Mária and Rosta, Judit},
	booktitle = {12th Congress of the European Pain Federation EFIC 2022-04-27 [Dublin, Írország]},
	unique-id = {33076058},
	year = {2022},
	pages = {1055},
	orcid-numbers = {Dux, Mária/0000-0002-9941-8188}
}

@article{MTMT:32952219,
	title = {Perineural Capsaicin Treatment Inhibits Collateral Sprouting of Intact Cutaneous Nociceptive Afferents},
	url = {https://m2.mtmt.hu/api/publication/32952219},
	author = {Sántha, Péter and Lakatos, Szandra and Horváth, Ágnes Judit and Dux, Mária and Jancsó, Gábor},
	doi = {10.3390/biomedicines10061326},
	journal-iso = {BIOMEDICINES},
	journal = {BIOMEDICINES},
	volume = {10},
	unique-id = {32952219},
	abstract = {Perineural treatment of peripheral nerves with capsaicin produces a long-lasting selective regional thermo- and chemo-analgesia and elimination of the neurogenic inflammatory response involving degeneration of nociceptive afferent fibers. In this study, we examined longitudinal changes in mustard oil-induced sensory neurogenic vasodilatation and plasma extravasation following perineural capsaicin treatment of the rat saphenous nerve utilizing scanning laser Doppler imaging and vascular labeling with colloidal silver. Capsaicin treatment resulted in a marked decrease in mustard oil-induced vasodilatation in the skin area served by the saphenous nerve. Repeated imaging of the vasodilatatory response showed no recovery for at least 7 weeks. However, following transection and ligation of the capsaicin-treated saphenous nerve, a substantial recovery of the vasodilatatory response was observed, suggesting a reinnervation of the chemodenervated skin area by collateral sprouting of neighboring intact sciatic nerve afferents. Elimination of the recovered vascular reaction by capsaicin treatment of the sciatic nerve supported this conclusion. Similar results have been obtained by using the vascular labeling technique. These findings indicate an inhibitory effect of persisting cutaneous nerve fibers on the collateral sprouting of intact nerve fibers into the chemodenervated skin area. These observations may bear implications for the development of sensory disturbances following peripheral nerve injuries.},
	keywords = {NEUROGENIC INFLAMMATION; TRPA1; collateral sprouting; capsaicin TRPV1; scanning laser Doppler perfusion imaging},
	year = {2022},
	eissn = {2227-9059},
	orcid-numbers = {Sántha, Péter/0000-0003-0552-0358; Horváth, Ágnes Judit/0000-0003-3964-0729; Dux, Mária/0000-0002-9941-8188; Jancsó, Gábor/0000-0002-0496-3416}
}