Skip to main content
Journal cover image

OnabotulinumtoxinA effects on trigeminal nociceptors.

Publication ,  Journal Article
Moore, AA; Nelson, M; Wickware, C; Choi, S; Moon, G; Xiong, E; Orta, L; Brideau-Andersen, A; Brin, MF; Broide, RS; Liedtke, W; Moore, C
Published in: Cephalalgia
February 2023

BACKGROUND: OnabotulinumtoxinA (onabotA) is approved globally for prevention of chronic migraine; however, the classical mechanism of action of onabotA in motor and autonomic neurons cannot fully explain the effectiveness of onabotulinumtoxinA in this sensory neurological disease. We sought to explore the direct effects of onabotulinumtoxinA on mouse trigeminal ganglion sensory neurons using an inflammatory soup-based model of sensitization. METHODS: Primary cultured trigeminal ganglion neurons were pre-treated with inflammatory soup, then treated with onabotulinumtoxinA (2.75 pM). Treated neurons were used to examine transient receptor potential vanilloid subtype 1 and transient receptor potential ankyrin 1 cell-surface expression, calcium influx, and neuropeptide release. RESULTS: We found that onabotulinumtoxinA cleaved synaptosomal-associated protein-25 kDa in cultured trigeminal ganglion neurons; synaptosomal-associated protein-25 kDa cleavage was enhanced by inflammatory soup pre-treatment, suggesting greater uptake of toxin under sensitized conditions. OnabotulinumtoxinA also prevented inflammatory soup-mediated increases in TRPV1 and TRPA1 cell-surface expression, without significantly altering TRPV1 or TRPA1 protein expression in unsensitized conditions. We observed similar inhibitory effects of onabotulinumtoxinA on TRP-mediated calcium influx and TRPV1- and TRPA1-mediated release of calcitonin gene-related peptide and prostaglandin 2 under sensitized, but not unsensitized control, conditions. CONCLUSIONS: Our data deepen the understanding of the sensory mechanism of action of onabotulinumtoxinA and support the notion that, once endocytosed, the cytosolic light chain of onabotulinumtoxinA cleaves synaptosomal-associated protein-25 kDa to prevent soluble N-ethylmaleimide-sensitive factor attachment protein receptor-mediated processes more generally in motor, autonomic, and sensory neurons.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Cephalalgia

DOI

EISSN

1468-2982

Publication Date

February 2023

Volume

43

Issue

2

Start / End Page

3331024221141683

Location

England

Related Subject Headings

  • Trigeminal Ganglion
  • Transient Receptor Potential Channels
  • TRPV Cation Channels
  • TRPA1 Cation Channel
  • Sensory Receptor Cells
  • Nociceptors
  • Neurology & Neurosurgery
  • Mice
  • Calcium
  • Botulinum Toxins, Type A
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Moore, A. A., Nelson, M., Wickware, C., Choi, S., Moon, G., Xiong, E., … Moore, C. (2023). OnabotulinumtoxinA effects on trigeminal nociceptors. Cephalalgia, 43(2), 3331024221141683. https://doi.org/10.1177/03331024221141683
Moore, Ashley A., Mariana Nelson, Christopher Wickware, Shinbe Choi, Gene Moon, Emma Xiong, Lily Orta, et al. “OnabotulinumtoxinA effects on trigeminal nociceptors.Cephalalgia 43, no. 2 (February 2023): 3331024221141683. https://doi.org/10.1177/03331024221141683.
Moore AA, Nelson M, Wickware C, Choi S, Moon G, Xiong E, et al. OnabotulinumtoxinA effects on trigeminal nociceptors. Cephalalgia. 2023 Feb;43(2):3331024221141683.
Moore, Ashley A., et al. “OnabotulinumtoxinA effects on trigeminal nociceptors.Cephalalgia, vol. 43, no. 2, Feb. 2023, p. 3331024221141683. Pubmed, doi:10.1177/03331024221141683.
Moore AA, Nelson M, Wickware C, Choi S, Moon G, Xiong E, Orta L, Brideau-Andersen A, Brin MF, Broide RS, Liedtke W, Moore C. OnabotulinumtoxinA effects on trigeminal nociceptors. Cephalalgia. 2023 Feb;43(2):3331024221141683.
Journal cover image

Published In

Cephalalgia

DOI

EISSN

1468-2982

Publication Date

February 2023

Volume

43

Issue

2

Start / End Page

3331024221141683

Location

England

Related Subject Headings

  • Trigeminal Ganglion
  • Transient Receptor Potential Channels
  • TRPV Cation Channels
  • TRPA1 Cation Channel
  • Sensory Receptor Cells
  • Nociceptors
  • Neurology & Neurosurgery
  • Mice
  • Calcium
  • Botulinum Toxins, Type A