The effect of orofacial complete Freund’s adjuvant treatment on the expression of migraine-related molecules
Abstract Background Migraine is a neurovascular primary headache disorder, which causes significant socioeconomic problems worldwide. The pathomechanism of disease is enigmatic, but activation of the trigeminovascular system (TS) appears to be essential during the attack. Migraine research of recent...
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doaj-f364f8c0359e47788f4d4ce9acd7318b2020-11-25T03:28:49ZengBMCThe Journal of Headache and Pain1129-23691129-23772019-04-012011910.1186/s10194-019-0999-7The effect of orofacial complete Freund’s adjuvant treatment on the expression of migraine-related moleculesTamás Körtési0Bernadett Tuka1Aliz Nyári2László Vécsei3János Tajti4Department of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center University of SzegedMTA-SZTE Neuroscience Research Group, University of SzegedDepartment of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center University of SzegedMTA-SZTE Neuroscience Research Group, University of SzegedDepartment of Neurology, Faculty of Medicine, Albert Szent-Györgyi Clinical Center University of SzegedAbstract Background Migraine is a neurovascular primary headache disorder, which causes significant socioeconomic problems worldwide. The pathomechanism of disease is enigmatic, but activation of the trigeminovascular system (TS) appears to be essential during the attack. Migraine research of recent years has focused on neuropeptides, such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide 1–38 (PACAP1–38) as potential pathogenic factors and possible therapeutic offensives. The goal of present study was to investigate the simultaneous expression of CGRP and precursor of PACAP1–38 (preproPACAP) in the central region of the TS in a time-dependent manner following TS activation in rats. Methods The right whisker pad of rats was injected with 50 μl Complete Freund’s Adjuvant (CFA) or saline. A mechanical allodynia test was performed with von Frey filaments before and after treatment. Transcardial perfusion of the animals was initiated 24, 48, 72 and 120 h after injection, followed by the dissection of the nucleus trigeminus caudalis (TNC). After preparation, the samples were stored at − 80 °C until further use. The relative optical density of CGRP and preproPACAP was analyzed by Western blot. One-way ANOVA and Kruskal-Wallis followed by Tukey post hoc test were used to evaluate the data. Regression analysis was applied to explore the correlation between neuropeptides expression and hyperalgesia. Results Orofacial CFA injection resulted in significant CGRP and preproPACAP release in the TNC 24, 48, 72 and 120 h after the treatment. The level of neuropeptides reached its maximum at 72 h after CFA injection, corresponding to the peak of facial allodynia. Negative, linear correlation was detected between the expression level of neuropeptides and value of mechanonociceptive threshold. Conclusion This is the first study which suggests that the expression of CGRP and preproPACAP simultaneously increases in the central region of activated TS and it influences the formation of mechanical hyperalgesia. Our results contribute to a better understanding of migraine pathogenesis and thereby to the development of more effective therapeutic approaches.http://link.springer.com/article/10.1186/s10194-019-0999-7MigraineTrigeminovascular systemCFACGRPpreproPACAP |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tamás Körtési Bernadett Tuka Aliz Nyári László Vécsei János Tajti |
spellingShingle |
Tamás Körtési Bernadett Tuka Aliz Nyári László Vécsei János Tajti The effect of orofacial complete Freund’s adjuvant treatment on the expression of migraine-related molecules The Journal of Headache and Pain Migraine Trigeminovascular system CFA CGRP preproPACAP |
author_facet |
Tamás Körtési Bernadett Tuka Aliz Nyári László Vécsei János Tajti |
author_sort |
Tamás Körtési |
title |
The effect of orofacial complete Freund’s adjuvant treatment on the expression of migraine-related molecules |
title_short |
The effect of orofacial complete Freund’s adjuvant treatment on the expression of migraine-related molecules |
title_full |
The effect of orofacial complete Freund’s adjuvant treatment on the expression of migraine-related molecules |
title_fullStr |
The effect of orofacial complete Freund’s adjuvant treatment on the expression of migraine-related molecules |
title_full_unstemmed |
The effect of orofacial complete Freund’s adjuvant treatment on the expression of migraine-related molecules |
title_sort |
effect of orofacial complete freund’s adjuvant treatment on the expression of migraine-related molecules |
publisher |
BMC |
series |
The Journal of Headache and Pain |
issn |
1129-2369 1129-2377 |
publishDate |
2019-04-01 |
description |
Abstract Background Migraine is a neurovascular primary headache disorder, which causes significant socioeconomic problems worldwide. The pathomechanism of disease is enigmatic, but activation of the trigeminovascular system (TS) appears to be essential during the attack. Migraine research of recent years has focused on neuropeptides, such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide 1–38 (PACAP1–38) as potential pathogenic factors and possible therapeutic offensives. The goal of present study was to investigate the simultaneous expression of CGRP and precursor of PACAP1–38 (preproPACAP) in the central region of the TS in a time-dependent manner following TS activation in rats. Methods The right whisker pad of rats was injected with 50 μl Complete Freund’s Adjuvant (CFA) or saline. A mechanical allodynia test was performed with von Frey filaments before and after treatment. Transcardial perfusion of the animals was initiated 24, 48, 72 and 120 h after injection, followed by the dissection of the nucleus trigeminus caudalis (TNC). After preparation, the samples were stored at − 80 °C until further use. The relative optical density of CGRP and preproPACAP was analyzed by Western blot. One-way ANOVA and Kruskal-Wallis followed by Tukey post hoc test were used to evaluate the data. Regression analysis was applied to explore the correlation between neuropeptides expression and hyperalgesia. Results Orofacial CFA injection resulted in significant CGRP and preproPACAP release in the TNC 24, 48, 72 and 120 h after the treatment. The level of neuropeptides reached its maximum at 72 h after CFA injection, corresponding to the peak of facial allodynia. Negative, linear correlation was detected between the expression level of neuropeptides and value of mechanonociceptive threshold. Conclusion This is the first study which suggests that the expression of CGRP and preproPACAP simultaneously increases in the central region of activated TS and it influences the formation of mechanical hyperalgesia. Our results contribute to a better understanding of migraine pathogenesis and thereby to the development of more effective therapeutic approaches. |
topic |
Migraine Trigeminovascular system CFA CGRP preproPACAP |
url |
http://link.springer.com/article/10.1186/s10194-019-0999-7 |
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