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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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