Acute neuroendocrine challenge elicits enhanced cortisol response and parallel transcriptomic changes in patients with migraine
Abstract. Introduction:. Migraine is a neurological disorder with recurrent attacks characterized by headaches and sensitivity to stimuli. Stress is a significant trigger for attacks; however, molecular mechanisms of the connection are poorly understood. Objectives:. To better characterize such mech...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer
2025-06-01
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| Series: | PAIN Reports |
| Online Access: | http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000001254 |
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| author | Sahel Kumar Peter Petschner Kinga Gecse Dora Torok Gabriella Juhasz |
| author_facet | Sahel Kumar Peter Petschner Kinga Gecse Dora Torok Gabriella Juhasz |
| author_sort | Sahel Kumar |
| collection | DOAJ |
| description | Abstract. Introduction:. Migraine is a neurological disorder with recurrent attacks characterized by headaches and sensitivity to stimuli. Stress is a significant trigger for attacks; however, molecular mechanisms of the connection are poorly understood.
Objectives:. To better characterize such mechanisms, we performed a placebo-controlled, double-blind crossover study with 51 participants (21 patients with migraine without aura and 30 healthy controls).
Methods:. Participants received a low-dose citalopram- or placebo challenge on 2 separate days. Prechallenge and postchallenge assessment of cortisol concentrations and transcriptomic changes using RNA-seq was performed from whole blood samples. Analysis of an accidental attack following the citalopram challenge was also conducted.
Results:. Neuroendocrine challenge elicited elevated cortisol concentrations at 30 (P-value = 0.1355) and 70 minutes (P-value = 0.07292) postchallenge in patients with migraine compared with controls. Gene expression analysis showed 10 differentially expressed genes (2 down- and 8 upregulated, P-value ≤ 0.005) and 10 dysregulated gene sets (P-value ≤ 0.005). Among them, dysregulated IKBKGP1 and NKRF genes and upregulated protein synthesis and translation, carbohydrate metabolism, and, attack-related, glycosylation can be highlighted.
Conclusion:. Patients with migraine without aura showed an enhanced cortisol response to a neuroendocrine challenge. This was accompanied by a probable suppression of NFκB activity through dysregulation of NKRF and an altered immune function. Upregulated carbohydrate metabolism may reflect the elevated cortisol concentrations' stimulating effects on endothelial glycocalyx, playing a role in NO-induced vasodilation, a trigger for migraine attacks. The results suggest the elevated cortisol response may trigger migraine attacks through altered glycocalyx and immune functions. |
| format | Article |
| id | doaj-art-501fb3e7c4f24db1bc71d13118db20ca |
| institution | OA Journals |
| issn | 2471-2531 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | PAIN Reports |
| spelling | doaj-art-501fb3e7c4f24db1bc71d13118db20ca2025-08-20T01:57:01ZengWolters KluwerPAIN Reports2471-25312025-06-01103e125410.1097/PR9.0000000000001254PR90000000000001254Acute neuroendocrine challenge elicits enhanced cortisol response and parallel transcriptomic changes in patients with migraineSahel Kumar0Peter Petschner1Kinga Gecse2Dora Torok3Gabriella Juhasz4a Department of Pharmacodynamics, Faculty of Pharmaceutical Sciences, Semmelweis University, Budapest, Hungarya Department of Pharmacodynamics, Faculty of Pharmaceutical Sciences, Semmelweis University, Budapest, Hungarya Department of Pharmacodynamics, Faculty of Pharmaceutical Sciences, Semmelweis University, Budapest, Hungarya Department of Pharmacodynamics, Faculty of Pharmaceutical Sciences, Semmelweis University, Budapest, Hungarya Department of Pharmacodynamics, Faculty of Pharmaceutical Sciences, Semmelweis University, Budapest, HungaryAbstract. Introduction:. Migraine is a neurological disorder with recurrent attacks characterized by headaches and sensitivity to stimuli. Stress is a significant trigger for attacks; however, molecular mechanisms of the connection are poorly understood. Objectives:. To better characterize such mechanisms, we performed a placebo-controlled, double-blind crossover study with 51 participants (21 patients with migraine without aura and 30 healthy controls). Methods:. Participants received a low-dose citalopram- or placebo challenge on 2 separate days. Prechallenge and postchallenge assessment of cortisol concentrations and transcriptomic changes using RNA-seq was performed from whole blood samples. Analysis of an accidental attack following the citalopram challenge was also conducted. Results:. Neuroendocrine challenge elicited elevated cortisol concentrations at 30 (P-value = 0.1355) and 70 minutes (P-value = 0.07292) postchallenge in patients with migraine compared with controls. Gene expression analysis showed 10 differentially expressed genes (2 down- and 8 upregulated, P-value ≤ 0.005) and 10 dysregulated gene sets (P-value ≤ 0.005). Among them, dysregulated IKBKGP1 and NKRF genes and upregulated protein synthesis and translation, carbohydrate metabolism, and, attack-related, glycosylation can be highlighted. Conclusion:. Patients with migraine without aura showed an enhanced cortisol response to a neuroendocrine challenge. This was accompanied by a probable suppression of NFκB activity through dysregulation of NKRF and an altered immune function. Upregulated carbohydrate metabolism may reflect the elevated cortisol concentrations' stimulating effects on endothelial glycocalyx, playing a role in NO-induced vasodilation, a trigger for migraine attacks. The results suggest the elevated cortisol response may trigger migraine attacks through altered glycocalyx and immune functions.http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000001254 |
| spellingShingle | Sahel Kumar Peter Petschner Kinga Gecse Dora Torok Gabriella Juhasz Acute neuroendocrine challenge elicits enhanced cortisol response and parallel transcriptomic changes in patients with migraine PAIN Reports |
| title | Acute neuroendocrine challenge elicits enhanced cortisol response and parallel transcriptomic changes in patients with migraine |
| title_full | Acute neuroendocrine challenge elicits enhanced cortisol response and parallel transcriptomic changes in patients with migraine |
| title_fullStr | Acute neuroendocrine challenge elicits enhanced cortisol response and parallel transcriptomic changes in patients with migraine |
| title_full_unstemmed | Acute neuroendocrine challenge elicits enhanced cortisol response and parallel transcriptomic changes in patients with migraine |
| title_short | Acute neuroendocrine challenge elicits enhanced cortisol response and parallel transcriptomic changes in patients with migraine |
| title_sort | acute neuroendocrine challenge elicits enhanced cortisol response and parallel transcriptomic changes in patients with migraine |
| url | http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000001254 |
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