Special Issue "Botulinum Toxin Treatment for Spasticity and Pain"

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

Deadline for manuscript submissions: 30 November 2021.

Special Issue Editor

Dr. Domenico Intiso
E-Mail
Guest Editor
Unit of Neuro-Rehabilitation and Rehabilitation Medicine, IRCCS ‘Casa Sollievo della Sofferenza’, Viale dei Cappuccini, San Giovanni Rotondo, 71013 Foggia, Italy
Interests: rehabilitation; brain injury; stroke; spasticity; critical illness polyneuropathy; acquired severe brain injury; outcome

Special Issue Information

Dear Colleagues,

Spasticity is a troublesome disorder that may occur in subjects after central nervous system (CNS) damage following stroke, brain injury, spinal cord injury, multiple sclerosis, and cerebral palsy. Likewise, pain may be a challenging complaint in several diseases that affect the nervous system and may be coexistent with spasticity.

Spasticity can hamper the rehabilitation process and contributes to the loss of motor dexterity and ability by promoting pain, persistent abnormal postures, articular limitations, and muscular–tendon contractures. Pain and spasticity, if untreated, can lead to discomfort, decreased functioning and participation, and poor self-esteem and quality of life.

Although several pharmacological and not pharmacological treatments have been used in managing spasticity, botulinum toxin (BoNT) is the first line of therapy in focal spasticity. However, several questions remain unclear that encompass pathophysiological mechanisms (peripheral and central), modality of administration, site (single or multiple levels), dilution, severity of spasticity and dosage (high dosage), adjunct tools (cast, exercises, electrical stimulation), and the effect on functional recovery.

Therapies in treating pain and neuropathic pain may be poorly effective. BoNT has been proposed as a promising and efficacious therapeutic strategy, but likewise and even more so than spasticity treatment, many questions and issues remain unsolved.

This Special Issue will focus the role of BoNT in the management of spasticity and pain, addressing unclear questions and new approaches. 

Dr. Domenico Intiso
Guest Editor

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Keywords

  • botulinum toxin
  • spasticity
  • rehabilitation
  • pain
  • therapeutic strategies
  • stroke
  • nervous system

Published Papers (4 papers)

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Research

Article
Peripherally Administered Botulinum Toxin Type A Localizes Bilaterally in Trigeminal Ganglia of Animal Model
Toxins 2021, 13(10), 704; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13100704 - 05 Oct 2021
Viewed by 335
Abstract
Peripheral nerve injury leads to sensory ganglion hyperexcitation, which increases neurotransmitter release and neuropathic pain. Botulinum toxin type A (BoNT/A) regulates pain transmission by reducing neurotransmitter release, thereby attenuating neuropathic pain. Despite multiple studies on the use of BoNT/A for managing neuropathic pain [...] Read more.
Peripheral nerve injury leads to sensory ganglion hyperexcitation, which increases neurotransmitter release and neuropathic pain. Botulinum toxin type A (BoNT/A) regulates pain transmission by reducing neurotransmitter release, thereby attenuating neuropathic pain. Despite multiple studies on the use of BoNT/A for managing neuropathic pain in the orofacial region, its exact mechanism of transport remains unclear. In this study, we investigated the effects of BoNT/A in managing neuropathic pain in two different animal models and its transport mechanism in the trigeminal nerve. Intraperitoneal administration of cisplatin induced bilateral neuropathic pain in the orofacial region, reducing the head withdrawal threshold to mechanical stimulation. Unilateral infraorbital nerve constriction (IONC) also reduced the ipsilateral head withdrawal threshold to mechanical stimulation. Unilateral peripheral administration of BoNT/A to the rat whisker pad attenuated cisplatin-induced pain behavior bilaterally. Furthermore, contralateral peripheral administration of BoNT/A attenuated neuropathy-induced behavior caused by IONC. We also noted the presence of BoNT/A in the blood using the mouse bioassay. In addition, the Alexa Fluor-488-labeled C-terminal half of the heavy chain of BoNT/A (BoNT/A-Hc) was localized in the neurons of the bilateral trigeminal ganglia following its unilateral administration. These findings suggest that axonal and hematogenous transport are involved in the therapeutic effects of peripherally administered BoNT/A in the orofacial region. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Spasticity and Pain)
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Article
Early Botulinum Toxin Type A Injection for Post-Stroke Spasticity: A Longitudinal Cohort Study
Toxins 2021, 13(6), 374; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13060374 - 24 May 2021
Cited by 1 | Viewed by 1257
Abstract
Early management of spasticity may improve stroke outcome. Botulinum toxin type A (BoNT-A) is recommended treatment for post-stroke spasticity (PSS). However, it is usually administered in the chronic phase of stroke. Our aim was to determine whether the length of time between stroke [...] Read more.
Early management of spasticity may improve stroke outcome. Botulinum toxin type A (BoNT-A) is recommended treatment for post-stroke spasticity (PSS). However, it is usually administered in the chronic phase of stroke. Our aim was to determine whether the length of time between stroke onset and initial BoNT-A injection has an effect on outcomes after PSS treatment. This multicenter, longitudinal, cohort study included stroke patients (time since onset <12 months) with PSS who received BoNT-A for the first time according to routine practice. The main outcome was the modified Ashworth scale (MAS). Patients were evaluated before BoNT-A injection and then at 4, 12, and 24 weeks of follow-up. Eighty-three patients with PSS were enrolled. MAS showed a significant decrease in PSS at 4 and 12 weeks but not at 24 weeks after treatment. Among the patients with a time between stroke onset and BoNT-A injection >90 days, the MAS were higher at 4 and 12 weeks than at 24 weeks compared to those injected ≤90 days since stroke. Our findings suggest that BoNT-A treatment for PSS should be initiated within 3 months after stroke onset in order to obtain a greater reduction in muscle tone at 1 and 3 months afterwards. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Spasticity and Pain)
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Article
Changes in Muscle Mass after Botulinum Toxin Injection in Children with Spastic Hemiplegic Cerebral Palsy
Toxins 2021, 13(4), 278; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13040278 - 14 Apr 2021
Viewed by 564
Abstract
We aimed to evaluate muscle mass changes after injection of botulinum toxin (BoNT) in children with spastic hemiplegic cerebral palsy (CP). Children aged between 2 and 12 years who were diagnosed with hemiplegic CP with spastic equinus foot were prospectively recruited and administered [...] Read more.
We aimed to evaluate muscle mass changes after injection of botulinum toxin (BoNT) in children with spastic hemiplegic cerebral palsy (CP). Children aged between 2 and 12 years who were diagnosed with hemiplegic CP with spastic equinus foot were prospectively recruited and administered BoNT in the affected leg. Lean body mass (LBM) of both legs and total limbs was measured by dual-energy X-ray absorptiometry (DXA) preinjection and 4 and 12 weeks after injection. A total of 15 children were enrolled into the study. LBM of both legs and total limbs increased significantly over 12 weeks of growth. The ratio of LBM of the affected leg to total limbs and to the unaffected leg significantly reduced at 4 weeks after injection compared with preinjection but significantly increased at 12 weeks after injection compared with 4 weeks after injection. In conclusion, the muscle mass of the affected leg after BoNT injection in children with hemiplegic spastic CP decreased at 4 weeks after BoNT injection but significantly recovered after 12 weeks after injection. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Spasticity and Pain)
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Article
BoNT-A for Post-Stroke Spasticity: Guidance on Unmet Clinical Needs from a Delphi Panel Approach
Toxins 2021, 13(4), 236; https://0-doi-org.brum.beds.ac.uk/10.3390/toxins13040236 - 25 Mar 2021
Viewed by 771
Abstract
There is extensive literature supporting the efficacy of botulinum toxin (BoNT-A) for the treatment of post-stroke spasticity, however, there remain gaps in the routine management of patients with post-stroke spasticity. A panel of 21 Italian experts was selected to participate in this web-based [...] Read more.
There is extensive literature supporting the efficacy of botulinum toxin (BoNT-A) for the treatment of post-stroke spasticity, however, there remain gaps in the routine management of patients with post-stroke spasticity. A panel of 21 Italian experts was selected to participate in this web-based survey Delphi process to provide guidance that can support clinicians in the decision-making process. There was a broad consensus among physicians that BoNT-A intervention should be administered as soon as the spasticity interferes with the patients’ clinical condition. Patients monitoring is needed over time, a follow-up of 4–6 weeks is considered necessary. Furthermore, physicians agreed that treatment should be offered irrespective of the duration of the spasticity. The Delphi consensus also stressed the importance of patient-centered goals in order to satisfy the clinical needs of the patient regardless of time of onset or duration of spasticity. The findings arising from this Delphi process provide insights into the unmet needs in managing post-stroke spasticity from the clinician’s perspective and provides guidance for physicians for the utilization of BoNT-A for the treatment of post-stroke spasticity in daily practice. Full article
(This article belongs to the Special Issue Botulinum Toxin Treatment for Spasticity and Pain)
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