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Mapping Dural and Periosteal SV2C, a Botulinum Toxin A Receptor, in the Mouse
Anisa Dehghani1,2, Agustin Melo-Carrillo1,2, Andrew M Strassman1,2
1Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
Toxins
|October 28, 2025
Summary
Researchers found synaptic vesicle protein 2C (SV2C) receptors in dura and periosteum axons, suggesting a mechanism for onabotulinumtoxinA (onabotA) in migraine prevention. This discovery supports onabotA
Area of Science:
- Neuroscience
- Immunohistochemistry
- Migraine Pathophysiology
Background:
- Botulinum toxin A (BoNT/A) receptor presence in migraine-related cephalic areas is debated.
- OnabotulinumtoxinA (onabotA) is used for chronic migraine prevention, but its precise action sites are unclear.
Purpose of the Study:
- To investigate the presence of synaptic vesicle protein 2C (SV2C), a potential onabotA receptor, in axons of the dura and periosteum.
- To map the distribution of SV2C-containing axons in these cranial structures.
Main Methods:
- Utilized single- and double-labeling immunohistochemical techniques in mouse models.
- Mapped and characterized the distribution of SV2C-positive axons within the dura mater and periosteum.
Main Results:
- Identified dense networks of SV2C-containing axons throughout the dura and periosteum.
- SV2C-LIR axons constituted significant portions of peripherin-, CGRP-, and NaV1.8-LIR fibers in both tissues, indicating sensory and possibly parasympathetic origins.
Conclusions:
- Findings suggest SV2C receptors are abundant in peripheral nerve axons, including sensory nociceptors, within the dura and periosteum.
- This provides a rationale for onabotA's efficacy in chronic migraine treatment and suggests potential benefits of periosteal injections.

