Background & Aims

Trigeminal neuralgia (TN) presents as severe, recurrent facial pain paroxysms triggered by innocuous stimuli, with demyelination of trigeminal nerve afferents as the primary hypothesis.(1,2) Recent studies emphasize the role of inflammation, urging a deeper understanding of neuroinflammation’s impact.(3–5) Despite limited evidence, onabotulinumtoxinA (BTX-A) shows promise for TN pain, potentially with anti-inflammatory effects and minimal side effects.(6–8) We aim to investigate the efficacy of BTX-A and the role of neuroinflammation in TN which would be globally impactful, potentially changing TN management and neuropathic pain understanding.

Methods

The study, an investigator-initiated randomized, placebo-controlled trial, aims to assess BTX-A efficacy in treating TN and the role of biomarkers. Eighty subjects randomized 1:1 for BTX-A or placebo (isotonic saline), will undergo a 4-week baseline followed by a 12-week double-blind evaluation. Responder status is defined as ?30% reduction in mean ADP during the evaluation period. Health-related quality of life and patient satisfaction will be measured using PENN-FPS-R and PGI-C scales. Blood and tear fluid samples, assessing biomarkers like CGRP and inflammatory markers, are taken before and after treatment.

Results

Eligible subjects, aged 18-85 with TN diagnosis, must be fluent in Danish. Exclusion criteria involve severe cardiovascular diseases and ongoing severe psychiatric issues. Botox® (BTX-A) 85U or placebo will be administered following a fixed dosage. Concomitant TN medications are allowed with stable doses, adhering to specific criteria.

Conclusions

We designed this study to assess the safety and efficacy of BTX-A, injected according to a standardized paradigm, either as preventive monotherapy or as an add-on treatment. Through a comprehensive approach, including patient-reported outcomes and biomarker analysis, the study could potentially bring valuable insights to TN management.

References

1.Olesen J. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1-211. doi:10.1177/0333102417738202
2.Bendtsen L, Zakrzewska JM, Heinskou TB, et al. Advances in diagnosis, classification, pathophysiology, and management of trigeminal neuralgia. Lancet Neurol 2020; 19: 784–796.
3.Ericson H, Hamdeh SA, Freyhult E, et al. Cerebrospinal fluid biomarkers of inflammation in trigeminal neuralgia patients operated with microvascular decompression. Pain. 2019;160(11):2603-2611. doi:10.1097/j.pain.0000000000001649.
4.Yao Y, Chang B, Li S. Relationship of Inflammation With Trigeminal Neuralgia. Journal of Craniofacial Surgery. 2020;31(2):E110-E113. doi:10.1097/SCS.0000000000005879.
5.Gerwin R. Chronic Facial Pain: Trigeminal Neuralgia, Persistent Idiopathic Facial Pain, and Myofascial Pain Syndrome—An Evidence-Based Narrative Review and Etiological Hypothesis. Int J Environ Res Public Health. 2020;17(19):7012. doi:10.3390/ijerph17197012.
6.Durham PL, Cady R, Cady R, Blumenfeld AJ. Regulation of Calcitonin Gene-Related Peptide Secretion from Trigeminal Nerve Cells by Botulinum Toxin Type A: Implications for Migraine Therapy. Headache. 2004;44(1):35-43. doi:10.1111/j.1526-4610.2004.04007.x
7.Gfrerer L, Xu W, Austen Jr W, et al. OnabotulinumtoxinA alters inflammatory gene expression and immune cells in chronic headache patients. Brain. 2022;145(7):2436-2449. doi:10.1093/brain/awab461
8.Burstein R, Blumenfeld AM, Silberstein SD, Manack Adams A, Brin MF. Mechanism of Action of OnabotulinumtoxinA in Chronic Migraine: A Narrative Review. Headache. 2020;60(7):1259-1272. doi:10.1111/head.13849

Presenting Author

Jacob Worm

Poster Authors

Jacob Worm

MD

Danish Headache Center, Copenhagen Uni. Hospital and University of Copenhagen

Lead Author

Niklas Rye Jørgensen

DMSc

Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet

Lead Author

Stine Maarbjerg

PhD

Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet

Lead Author

Lars Bendtsen

DMSc

Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet

Lead Author

Henrik Winther Schytz

DMSc

Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet

Lead Author

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Orofacial Pain