Peripherally administered botulinum toxin type a localizes bilaterally in trigeminal ganglia of animal model

Arief Waskitho, Yumiko Yamamoto, Swarnalakshmi Raman, Fumiya Kano, Huijiao Yan, Resmi Raju, Shaista Afroz, Tsuyoshi Morita, Daisuke Ikutame, Kazuo Okura, Masamitsu Oshima, Akihito Yamamoto, Otto Baba, Yoshizo Matsuka

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

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 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 Cterminal 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.

Original languageEnglish
Article number704
JournalToxins
Volume13
Issue number10
DOIs
Publication statusPublished - Oct 2021
Externally publishedYes

Keywords

  • Botulinum toxin
  • Neuropathic pain
  • Trigeminal ganglion

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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