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Peripherally Administered Botulinum Toxin Type A Localizes Bilaterally in Trigeminal Ganglia of Animal Model
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 us...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541196/ https://www.ncbi.nlm.nih.gov/pubmed/34678997 http://dx.doi.org/10.3390/toxins13100704 |
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author | Waskitho, Arief Yamamoto, Yumiko Raman, Swarnalakshmi Kano, Fumiya Yan, Huijiao Raju, Resmi Afroz, Shaista Morita, Tsuyoshi Ikutame, Daisuke Okura, Kazuo Oshima, Masamitsu Yamamoto, Akihito Baba, Otto Matsuka, Yoshizo |
author_facet | Waskitho, Arief Yamamoto, Yumiko Raman, Swarnalakshmi Kano, Fumiya Yan, Huijiao Raju, Resmi Afroz, Shaista Morita, Tsuyoshi Ikutame, Daisuke Okura, Kazuo Oshima, Masamitsu Yamamoto, Akihito Baba, Otto Matsuka, Yoshizo |
author_sort | Waskitho, Arief |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8541196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85411962021-10-24 Peripherally Administered Botulinum Toxin Type A Localizes Bilaterally in Trigeminal Ganglia of Animal Model Waskitho, Arief Yamamoto, Yumiko Raman, Swarnalakshmi Kano, Fumiya Yan, Huijiao Raju, Resmi Afroz, Shaista Morita, Tsuyoshi Ikutame, Daisuke Okura, Kazuo Oshima, Masamitsu Yamamoto, Akihito Baba, Otto Matsuka, Yoshizo Toxins (Basel) Article 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. MDPI 2021-10-05 /pmc/articles/PMC8541196/ /pubmed/34678997 http://dx.doi.org/10.3390/toxins13100704 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Waskitho, Arief Yamamoto, Yumiko Raman, Swarnalakshmi Kano, Fumiya Yan, Huijiao Raju, Resmi Afroz, Shaista Morita, Tsuyoshi Ikutame, Daisuke Okura, Kazuo Oshima, Masamitsu Yamamoto, Akihito Baba, Otto Matsuka, Yoshizo Peripherally Administered Botulinum Toxin Type A Localizes Bilaterally in Trigeminal Ganglia of Animal Model |
title | Peripherally Administered Botulinum Toxin Type A Localizes Bilaterally in Trigeminal Ganglia of Animal Model |
title_full | Peripherally Administered Botulinum Toxin Type A Localizes Bilaterally in Trigeminal Ganglia of Animal Model |
title_fullStr | Peripherally Administered Botulinum Toxin Type A Localizes Bilaterally in Trigeminal Ganglia of Animal Model |
title_full_unstemmed | Peripherally Administered Botulinum Toxin Type A Localizes Bilaterally in Trigeminal Ganglia of Animal Model |
title_short | Peripherally Administered Botulinum Toxin Type A Localizes Bilaterally in Trigeminal Ganglia of Animal Model |
title_sort | peripherally administered botulinum toxin type a localizes bilaterally in trigeminal ganglia of animal model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541196/ https://www.ncbi.nlm.nih.gov/pubmed/34678997 http://dx.doi.org/10.3390/toxins13100704 |
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