Peripherally Administered Botulinum Toxin Type A Localizes Bilaterally in Trigeminal Ganglia of Animal Model

被引:11
作者
Waskitho, Arief [1 ]
Yamamoto, Yumiko [2 ]
Raman, Swarnalakshmi [1 ]
Kano, Fumiya [3 ]
Yan, Huijiao [1 ]
Raju, Resmi [4 ]
Afroz, Shaista [5 ]
Morita, Tsuyoshi [6 ]
Ikutame, Daisuke [1 ]
Okura, Kazuo [1 ]
Oshima, Masamitsu [1 ]
Yamamoto, Akihito [3 ]
Baba, Otto [6 ]
Matsuka, Yoshizo [1 ]
机构
[1] Tokushima Univ, Grad Sch Biomed Sci, Dept Stomatognath Funct & Occlusal Reconstruct, Tokushima 7708504, Japan
[2] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Bacteriol, Okayama 7008558, Japan
[3] Tokushima Univ, Grad Sch Biomed Sci, Dept Tissue Regenerat, Tokushima 7708504, Japan
[4] Natl Ctr Geriatr & Gerontol, Dept Oral Dis Res, Obu 4748511, Japan
[5] Aligarh Muslim Univ, ZA Dent Coll, Dept Prosthodont, Aligarh 202002, Uttar Pradesh, India
[6] Tokushima Univ, Grad Sch Biomed Sci, Dept Oral & Maxillofacial Anat, Tokushima 7708504, Japan
关键词
botulinum toxin; trigeminal ganglion; neuropathic pain; GENE-RELATED PEPTIDE; FUNCTIONAL RECOVERY; NEUROPATHIC PAIN; EVOKED RELEASE; NERVE INJURY; SUBSTANCE-P; NEUROTOXIN; HYPERALGESIA; DECREASES; NEURALGIA;
D O I
10.3390/toxins13100704
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
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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页数:11
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