The impact of the migraine treatment onabotulinumtoxinA on inflammatory and pain responses: Insights from an animal model
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Migraine, a prevalent and debilitating disease, involves complex pathophysiology possibly including inflammation and heightened pain sensitivity. The current study utilized the complete Freund's adjuvant (CFA) model of inflammation, with onabotulinumtoxinA (BoNT/A) as a treatment of interest due to its use in clinical migraine management. Using an animal model, the study sought to investigate the role of BoNT/A in modulating CFA-induced inflammation, alterations in pain sensitivity, and the regulation of calcitonin gene–related peptide (CGRP) release. Further, we aimed to assess the changes in SNAP-25 through western blot analysis to gain insights into the mechanistic action of BoNT/A.
Methods
BoNT/A or control was administered subcutaneously at the periorbital region of rats 3 days before the induction of inflammation using CFA. Periorbital mechanical sensitivity was assessed post-inflammation, and alterations in CGRP release were evaluated. Changes in SNAP-25 levels were determined using western blot analysis.
Results
Upon CFA-induced inflammation, there was a marked increase in periorbital mechanical sensitivity, with the inflammation side showing increased sensitivity compared to other periorbital areas. BoNT/A did decrease the withdrawal thresholds in the electronic von Frey test. Despite not being able to observe differences in pain thresholds or CGRP release, BoNT/A reduced baseline release under CFA inflamed conditions. Analysis of SNAP-25 levels in the trigeminal ganglion revealed both intact and cleaved forms that were notably elevated in BoNT/A-treated animals. These findings, derived from western blot analysis, suggest an effect on neurotransmitter release.
Conclusion
Our investigation highlights the role of BoNT/A in reducing baseline CGRP in the context of inflammation and its involvement in SNAP-25 cleavage. In contrast, BoNT/A did not appear to alter facial pain sensitivity induced by inflammation, suggesting that mechanisms other than baseline CGRP could be implicated in the elevated thresholds in the CFA model.
Originalsprog | Engelsk |
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Tidsskrift | Headache |
Vol/bind | 64 |
Udgave nummer | 6 |
Sider (fra-til) | 652-662 |
Antal sider | 11 |
ISSN | 0017-8748 |
DOI | |
Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:
and declare no conflicts of interest pertaining to the submitted work. received a research grant from Allergan to perform the present study. Philip Victor Reducha, Jesper Peter B\u00F6mers, Kristian Agmund Haanes Lars Edvinsson
Funding Information:
Kristian Agmund Haanes was supported by a Lundbeck Foundation Fellowship (R345\u20102020\u20101977). Lars Edvinsson received a research grant from Allergan to investigate the effect of BoNT/A in the inflammation model. The funders did not have any role during its execution, analyses, interpretation of the data, or decision to submit results.
Publisher Copyright:
© 2024 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.
ID: 391677575