The impact of the migraine treatment onabotulinumtoxinA on inflammatory and pain responses: Insights from an animal model

Philip Victor Reducha; Jesper Peter Bömers; Lars Edvinsson; Kristian Agmund Haanes

doi:10.1111/head.14726

The impact of the migraine treatment onabotulinumtoxinA on inflammatory and pain responses: Insights from an animal model

Headache. 2024 May 3. doi: 10.1111/head.14726. Online ahead of print.

Authors

Philip Victor Reducha^{1

2}, Jesper Peter Bömers^{1

3

4}, Lars Edvinsson^{3

4

5}, Kristian Agmund Haanes^{1

2}

Affiliations

¹ Sensory Biology Unit, Translational Research Centre, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.
² Section of Cell Biology and Physiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
³ Clinical Experimental Research Unit, Translational Research Centre, Copenhagen University Hospital - Rigshospitalet, Glostrup, Denmark.
⁴ Department of Neurosurgery, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
⁵ Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University Hospital, Lund, Sweden.

PMID: 38700141
DOI: 10.1111/head.14726

Abstract

Objective: 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.

Keywords: calcitonin gene–related peptide; inflammation; migraine; onabotulinumtoxinA; pain sensitivity.

Abstract

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