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Toxins
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Efficacy of Botulinum Toxin in Orofacial Pain
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Efficacy of Botulinum Toxin in Orofacial Pain

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".

Deadline for manuscript submissions: 30 September 2026 | Viewed by 1556

Special Issue Editors

Prof. Dr. Yoshizo Matsuka

E-Mail Website
Guest Editor
Department of Stomatognathic Function and Occlusal Reconstruction, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8504, Japan
Interests: botulinum toxin; mandibular movement; orofacial pain; oral reconstruction; neuropathic pain
Special Issues, Collections and Topics in MDPI journals
Dr. Swarnalakshmi Raman

E-Mail Website
Guest Editor
Department of Neural and Pain Science, University of Maryland Baltimore, Baltimore, MD 21201, USA
Interests: botulinum toxin; oral pathology; orofacial pain; temporomandibular joint pain

Special Issue Information

Dear Colleagues,

Orofacial pain, encompassing conditions such as temporomandibular disorders, neuropathic pain, and migraine, significantly affects patients’ quality of life. In recent decades, increasing amounts of data have shown that the Botulinum toxin is an effective and safe therapeutic tool for orofacial pain interventions.

Therefore, we are compiling this Special Issue of Toxins, entitled “Efficacy of Botulinum Toxin in Orofacial Pain”. This Special Issue aims to bring together the latest research on the effects of the Botulinum toxin in the management of pain in the facial and oral regions and their positive, as well as its therapeutic but also potentially negative clinical implications. Another aim is to elucidate the potential mechanisms involved in these central effects. We welcome contributions from clinicians and researchers in neurology, orofacial pain, dentistry, and related fields to participate in expanding the knowledge regarding the efficacy of the Botulinum toxin in orofacial pain. In this Special Issue, original research articles and reviews are both encouraged.

Prof. Dr. Yoshizo Matsuka
Dr. Swarnalakshmi Raman
Guest Editors

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a double-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • botulinum toxin
  • orofacial pain
  • neuropathic pain
  • trigeminal neuralgia
  • temporomandibular disorders
  • migraine
  • bruxism
  • myofascial pain
  • hemifacial spasm
  • orofacial dystonia
  • facial paralysis

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Published Papers (3 papers)

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Review

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17 pages, 2552 KB  
Review
Botulinumtoxin Type-A (BoNTA) in the Management of Refractory Trigeminal Neuralgia: An Expert-Opinion, Practice-Oriented Narrative Review on Behalf of the GRASP Study Group
by Andreas A. Argyriou, Emmanouil V. Dermitzakis, Dimitrios Rikos, Georgia Xiromerisiou, Panagiotis Soldatos, Maria Chondrogianni, Eleni Mavraki and Michail Vikelis
Toxins 2026, 18(6), 248; https://doi.org/10.3390/toxins18060248 - 29 May 2026
Abstract
Trigeminal neuralgia (TN) ranks among the most excruciating neuropathic pain syndromes, characterized clinically by multiple daily episodes of unilateral, paroxysmal, electric shock-like facial pain. The daily activities and quality of life of affected patients are profoundly diminished. First-line pharmacological agents, such as carbamazepine [...] Read more.
Trigeminal neuralgia (TN) ranks among the most excruciating neuropathic pain syndromes, characterized clinically by multiple daily episodes of unilateral, paroxysmal, electric shock-like facial pain. The daily activities and quality of life of affected patients are profoundly diminished. First-line pharmacological agents, such as carbamazepine and oxcarbazepine, provide initial relief for many patients. However, a significant proportion eventually develops refractory symptoms or experience intolerable adverse effects, leading to the discontinuation of traditional oral medications. For these patients with complex clinical phenotypes who fail to respond or are intolerant to these therapies, alternative pharmacological strategies are required before considering invasive surgical procedures. Over the past two decades, botulinumtoxin type-A (BoNTA) has become an effective and safe, minimally invasive therapeutic option for refractory TN. This review provides a practical framework for BoNTA use in the clinical setting of refractory TN. To connect the pathophysiological background with clinical patient care, we summarize the current understanding of TN pathophysiology, the proposed mechanisms by which BoNTA exerts its antinociceptive effects and the evolving clinical evidence supporting its efficacy and safety. We also critically examine dosing protocols, injection techniques, long-term outcomes and the integration of BoNTA into the management algorithm of refractory TN. Full article
(This article belongs to the Special Issue Efficacy of Botulinum Toxin in Orofacial Pain)
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10 pages, 238 KB  
Review
Botulinum Toxin for Chronic Migraine: Beyond Headache Reduction and Toward Possible Cognitive Benefits
by Mauro Silvestrini, Giovanna Viticchi, Sergio Salvemini, Gioacchino De Vanna, Marco Bartolini and Simona Luzzi
Toxins 2026, 18(4), 153; https://doi.org/10.3390/toxins18040153 - 24 Mar 2026
Viewed by 792
Abstract
Chronic migraine (CM) is a debilitating neurological disorder characterized not only by persistent and severe pain, but also by substantial cognitive dysfunction that affects attention, working memory, processing speed, and executive functions. These neuropsychological disturbances are likely influenced by overall disease burden and [...] Read more.
Chronic migraine (CM) is a debilitating neurological disorder characterized not only by persistent and severe pain, but also by substantial cognitive dysfunction that affects attention, working memory, processing speed, and executive functions. These neuropsychological disturbances are likely influenced by overall disease burden and are further modulated by affective comorbidities, sleep disturbances, and medication overuse. OnabotulinumtoxinA (BoNT-A) is an established preventive therapy for CM, supported by strong evidence of both efficacy and safety. This narrative review synthesizes findings from studies examining the relationship between BoNT-A treatment and domain-specific cognitive improvements in CM. It also outlines the potential pathophysiological mechanisms underlying these effects, summarizes the limitations of the existing literature, and highlights priorities for future research. Current evidence suggests that BoNT-A may confer neurocognitive benefits, particularly in working memory and processing speed, and that these improvements may occur partly independently of reductions in headache frequency. These favorable cognitive effects appear to be plausibly linked to decreased nociceptive “noise” and improved cortical inhibition, potentially mediated through modulation of central sensitization, nociceptive signaling, and affective states. Full article
(This article belongs to the Special Issue Efficacy of Botulinum Toxin in Orofacial Pain)

Other

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8 pages, 1348 KB  
Case Report
Subcutaneous Incobotulinumtoxin-A for Refractory Central Post-Stroke Neuropathic Pain: A Report of Two Cases
by Stefano Carda and Elisa Grana
Toxins 2026, 18(5), 217; https://doi.org/10.3390/toxins18050217 - 3 May 2026
Viewed by 343
Abstract
Background: Post-stroke neuropathic pain, particularly central post-stroke pain and facial pain syndromes, continues to be challenging to manage with conventional pharmacological approaches. While botulinum toxin A (BoNT-A) is well established for treating spasticity after stroke, its use in the management of central neuropathic [...] Read more.
Background: Post-stroke neuropathic pain, particularly central post-stroke pain and facial pain syndromes, continues to be challenging to manage with conventional pharmacological approaches. While botulinum toxin A (BoNT-A) is well established for treating spasticity after stroke, its use in the management of central neuropathic pain remains less well established. Methods: This report presents two cases of patients with refractory neuropathic pain following ischemic cerebrovascular accidents who achieved significant pain relief through subcutaneous botulinum toxin administration, after failure of multiple conventional and intramuscular BoNT-A approaches. Results: Case 1 involves a 66-year-old patient with 18 years of post-stroke hemicorporeal pain who responded dramatically to subcutaneous BoNT-A injections after extensive prior treatment failures. Case 2 describes a 54-year-old with trigeminal-region and mandibular pain following ICA dissection who achieved complete pain resolution at facial sites with subcutaneous administration of BoNT-A. Conclusions: These cases demonstrate the potential efficacy of subcutaneous botulinum toxin for managing post-stroke neuropathic pain in selected patients and suggest a mechanism of action related to peripheral pain sensitization rather than motor denervation. Our findings support further investigation of subcutaneous administration techniques for pain management in specialized centers. Full article
(This article belongs to the Special Issue Efficacy of Botulinum Toxin in Orofacial Pain)
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