Botulinum Toxins: Beyond the SNAP-25 Cleavage and New Insights on Pain Relief Mechanisms

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

Deadline for manuscript submissions: 31 December 2025 | Viewed by 1089

Special Issue Editors


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Guest Editor
The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK
Interests: botulism; botulinum neurotoxins; antitoxins; in vivo; ex vivo; cell based assays
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Guest Editor
Humana Biosciences-Prologue Biotech, 516 Rue Pierre et Marie Curie, 31670 Labège, France
Interests: botulinum neurotoxins; human cell based assays; ex vivo; in vivo; translational research

Special Issue Information

Dear Colleagues,

Botulinum neurotoxins (BoNTs) have become a well-established treatment option in a wide range of excessive muscle contractility disorders and as such have been routinely used since decades to treat cervical dystonia, spastic conditions, blepharospasm, hyperhidrosis, and for cosmetic purposes. BoNTs are categorized into seven toxinotypes, two of which are in clinical use, with each toxinotype being divided into multiple subtypes. With the development of bioinformatic tools, new BoNT-like toxins have been identified in non-Clostridial organisms, in addition to the expanding indications of existing formulations. The increased understanding of their molecular biology as well as the design of recombinant BoNT form the basis to develop innovative BoNT-based therapeutics as well as research tools. An overview of the diverse mechanisms of action of the BoNT family along with their impact on the nociceptive pathways, through its central and peripheral activities, the molecular mechanisms of action in neurons, and general pharmacokinetic parameters are presented in this Special Issue providing a broader understanding of its actions. This Special Issue will allow the advanced understanding of their therapeutic potential in acute and chronic pain, while further experimental and clinical research is still required to validate the mechanisms of action experimentally.

Dr. Christine Rasetti-Escargueil
Dr. Stefano Palea
Guest Editors

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Keywords

  • botulinum neurotoxin
  • SNAP-25
  • recombinant BoNTs
  • acute pain
  • chronic pain
  • visceral pain

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Published Papers (2 papers)

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Research

14 pages, 871 KiB  
Article
Variation in Subtypes of Obsessive-Compulsive Traits in Migraine Patients Undergoing Onabotulinum Toxin A Therapy
by Giovanna Viticchi, Lorenzo Falsetti, Chiara Di Felice, Gioacchino De Vanna, Sergio Salvemini, Marco Bartolini, Gianluca Moroncini and Mauro Silvestrini
Toxins 2025, 17(4), 199; https://doi.org/10.3390/toxins17040199 - 14 Apr 2025
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Abstract
Background: Patients with chronic migraine (CM) associated with medication overuse headache (MOH) often exhibit concomitant psychiatric traits including obsessive-compulsive disorder (OCD). Limited data exist on the impact of migraine therapies on these traits. This study aimed to analyse the influence of onabotulinum toxin [...] Read more.
Background: Patients with chronic migraine (CM) associated with medication overuse headache (MOH) often exhibit concomitant psychiatric traits including obsessive-compulsive disorder (OCD). Limited data exist on the impact of migraine therapies on these traits. This study aimed to analyse the influence of onabotulinum toxin A (OBT-A) on OCD in CM + MOH patients. Methods: All CM + MOH patients attending the AOU-Marche Headache Centre and treated with OBT-A over a 9-month period were prospectively analysed. At baseline and every three months, patients completed several questionnaires, including the Obsessive-Compulsive Inventory-Revised (OCI-R), to assess the presence of OCD and its subscales. Results: Thirty patients were enrolled. Repeated measures tests revealed a statistically significant decrease from T0 to T3 in the OCI-R score (p = 0.017) and among the different subscales, specifically the checking score (p = 0.029). The MIDAS (migraine disability assessment score) and HIT-6 (headache impact test) scores exhibited a statistically significant reduction from T0 to T3 (p < 0.0001), similar to the decrease in monthly migraine days and symptomatic medication intake. Conclusions: Patients treated with OBT-A showed significant improvement in OCD, particularly in subscales assessing somatic and aggressive obsessions as well as control compulsions. Several patients transitioned from a CM + MOH condition to an episodic form without drug abuse. The potential impact of OBT-A on psychiatric symptoms warrants further consideration to improve patient management strategies. Full article
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16 pages, 2122 KiB  
Article
Botulinum Toxin Type A Exerts Direct Trans-Synaptic Action at Bilateral Spinal Nociceptive Circuits
by Dalia Nemanić, Petra Šoštarić, Patrik Meglić, Ivica Matak and Lidija Bach-Rojecky
Toxins 2025, 17(3), 140; https://doi.org/10.3390/toxins17030140 - 14 Mar 2025
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Abstract
Botulinum toxin type A (BoNT-A) induces a bilateral analgesic effect following unilateral injection in rodent bilateral or mirror pain models. This occurs either by indirect plasticity-related actions, or by the toxin’s direct central action in bilateral spinal circuits. Herein, we aimed to resolve [...] Read more.
Botulinum toxin type A (BoNT-A) induces a bilateral analgesic effect following unilateral injection in rodent bilateral or mirror pain models. This occurs either by indirect plasticity-related actions, or by the toxin’s direct central action in bilateral spinal circuits. Herein, we aimed to resolve this question by assessing the role of trans-synaptic toxin traffic in a bilateral inflammatory pain model. The analgesic effect of the toxin was examined in rats pre-treated with unilateral intraplantar BoNT-A (7 U/kg) and subsequently challenged with bilateral carrageenan-evoked hind-paw inflammation (2%, 50 µL/paw, 6 days post BoNT-A). Specific neutralizing antitoxin injected into the lumbar intrathecal space (2 IU, 24 h post BoNT-A), aimed at preventing the spinal trans-synaptic traffic of BoNT-A, abolished its bilateral analgesic effect. The toxin trans-synaptic effect was associated with reduced c-Fos neuronal activation and BoNT-A-mediated cleavage of synaptosomal-associated protein 25 (SNAP-25) in the bilateral dorsal horn. Here, we showed that, in bilaterally occurring pain, BoNT-A exerts a direct contralateral analgesic action extending beyond the level of the dorsal root ganglion sensory neuron that directly links the hindlimb injection site to the primary sensory region. This points to the crucial role of the toxin’s central trans-synaptic traffic, and its direct action at propriospinal nociceptive circuits in its pain-relieving efficacy. Full article
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