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Antinociceptive Effects of Transcytosed Botulinum Neurotoxin Type A on Trigeminal Nociception in Rats.

Kim HJ, Lee GW, Kim MJ, Yang KY, Kim ST, Bae YC, Ahn DK - Korean J. Physiol. Pharmacol. (2015)

Bottom Line: Subcutaneous (3 U/kg) or intracisternal (0.3 or 1 U/kg) administration of BoNT-A significantly inhibited the formalin-induced nociceptive response in the second phase.These results suggest that the central antinociceptive effects the peripherally or centrally administered BoNT-A are mediated by transcytosed BoNT-A or direct inhibition of trigeminal neurons.Our data suggest that central targets of BoNT-A might provide a new therapeutic tool for the treatment of orofacial chronic pain conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.

ABSTRACT
We examined the effects of peripherally or centrally administered botulinum neurotoxin type A (BoNT-A) on orofacial inflammatory pain to evaluate the antinociceptive effect of BoNT-A and its underlying mechanisms. The experiments were carried out on male Sprague-Dawley rats. Subcutaneous (3 U/kg) or intracisternal (0.3 or 1 U/kg) administration of BoNT-A significantly inhibited the formalin-induced nociceptive response in the second phase. Both subcutaneous (1 or 3 U/kg) and intracisternal (0.3 or 1 U/kg) injection of BoNT-A increased the latency of head withdrawal response in the complete Freund's adjuvant (CFA)-treated rats. Intracisternal administration of N-methyl-D-aspartate (NMDA) evoked nociceptive behavior via the activation of trigeminal neurons, which was attenuated by the subcutaneous or intracisternal injection of BoNT-A. Intracisternal injection of NMDA up-regulated c-Fos expression in the trigeminal neurons of the medullary dorsal horn. Subcutaneous (3 U/kg) or intracisternal (1 U/kg) administration of BoNT-A significantly reduced the number of c-Fos immunoreactive neurons in the NMDA-treated rats. These results suggest that the central antinociceptive effects the peripherally or centrally administered BoNT-A are mediated by transcytosed BoNT-A or direct inhibition of trigeminal neurons. Our data suggest that central targets of BoNT-A might provide a new therapeutic tool for the treatment of orofacial chronic pain conditions.

No MeSH data available.


Related in: MedlinePlus

Effects of the subcutaneous or intracisternal injection of botulinum neurotoxin type A (BoNT-A) on c-Fos expression in the medullary dorsal horn. (A) c-Fos immunoreactive neurons in a naïve animal. (B) Intracisternal administration of 0.5 µg NMDA increased the number of c-Fos immunoreactive neurons in the superficial lamina I and II in the medullary dorsal horn. (C) Subcutaneous administration of BoNT-A (3 U/kg) decreased the number of c-Fos immunoreactive neurons. (D) Intracisternal injection of BoNT-A (1 U/kg) decreased the number of c-Fos immunoreactive neurons. (E) The histogram shows the number of c-Fos immunoreactive neurons in the ipsilateral medullary dorsal horn. *p<0.05 vehicle vs. BoNT-A treated group, n=5 animals per group. Scale bar, 100 µm.
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Figure 4: Effects of the subcutaneous or intracisternal injection of botulinum neurotoxin type A (BoNT-A) on c-Fos expression in the medullary dorsal horn. (A) c-Fos immunoreactive neurons in a naïve animal. (B) Intracisternal administration of 0.5 µg NMDA increased the number of c-Fos immunoreactive neurons in the superficial lamina I and II in the medullary dorsal horn. (C) Subcutaneous administration of BoNT-A (3 U/kg) decreased the number of c-Fos immunoreactive neurons. (D) Intracisternal injection of BoNT-A (1 U/kg) decreased the number of c-Fos immunoreactive neurons. (E) The histogram shows the number of c-Fos immunoreactive neurons in the ipsilateral medullary dorsal horn. *p<0.05 vehicle vs. BoNT-A treated group, n=5 animals per group. Scale bar, 100 µm.

Mentions: Effects of BoNT-A on c-Fos expression are illustrated in Fig. 4. Intracisternal injection of NMDA evoked intense rubbing. In addition to behavioral responses, intracisternal injection of 0.5 µg NMDA up-regulated c-Fos expression in the trigeminal neurons of the medullary dorsal horn. Most c-Fos-positive neurons were localized in the superficial layer (lamina I-II). Subcutaneous injection of BoNT-A (3 U/kg) significantly attenuated the number of c-Fos immunoreactive neurons induced by the intracisternal injection of NMDA (p<0.05, Fig. 4C). Additionally, intracisternal administration of BoNT-A (1 U/kg) significantly decreased the number of c-Fos immunoreactive neurons in the medullary dorsal horn (p<0.05, Fig. 4D).


Antinociceptive Effects of Transcytosed Botulinum Neurotoxin Type A on Trigeminal Nociception in Rats.

Kim HJ, Lee GW, Kim MJ, Yang KY, Kim ST, Bae YC, Ahn DK - Korean J. Physiol. Pharmacol. (2015)

Effects of the subcutaneous or intracisternal injection of botulinum neurotoxin type A (BoNT-A) on c-Fos expression in the medullary dorsal horn. (A) c-Fos immunoreactive neurons in a naïve animal. (B) Intracisternal administration of 0.5 µg NMDA increased the number of c-Fos immunoreactive neurons in the superficial lamina I and II in the medullary dorsal horn. (C) Subcutaneous administration of BoNT-A (3 U/kg) decreased the number of c-Fos immunoreactive neurons. (D) Intracisternal injection of BoNT-A (1 U/kg) decreased the number of c-Fos immunoreactive neurons. (E) The histogram shows the number of c-Fos immunoreactive neurons in the ipsilateral medullary dorsal horn. *p<0.05 vehicle vs. BoNT-A treated group, n=5 animals per group. Scale bar, 100 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4499647&req=5

Figure 4: Effects of the subcutaneous or intracisternal injection of botulinum neurotoxin type A (BoNT-A) on c-Fos expression in the medullary dorsal horn. (A) c-Fos immunoreactive neurons in a naïve animal. (B) Intracisternal administration of 0.5 µg NMDA increased the number of c-Fos immunoreactive neurons in the superficial lamina I and II in the medullary dorsal horn. (C) Subcutaneous administration of BoNT-A (3 U/kg) decreased the number of c-Fos immunoreactive neurons. (D) Intracisternal injection of BoNT-A (1 U/kg) decreased the number of c-Fos immunoreactive neurons. (E) The histogram shows the number of c-Fos immunoreactive neurons in the ipsilateral medullary dorsal horn. *p<0.05 vehicle vs. BoNT-A treated group, n=5 animals per group. Scale bar, 100 µm.
Mentions: Effects of BoNT-A on c-Fos expression are illustrated in Fig. 4. Intracisternal injection of NMDA evoked intense rubbing. In addition to behavioral responses, intracisternal injection of 0.5 µg NMDA up-regulated c-Fos expression in the trigeminal neurons of the medullary dorsal horn. Most c-Fos-positive neurons were localized in the superficial layer (lamina I-II). Subcutaneous injection of BoNT-A (3 U/kg) significantly attenuated the number of c-Fos immunoreactive neurons induced by the intracisternal injection of NMDA (p<0.05, Fig. 4C). Additionally, intracisternal administration of BoNT-A (1 U/kg) significantly decreased the number of c-Fos immunoreactive neurons in the medullary dorsal horn (p<0.05, Fig. 4D).

Bottom Line: Subcutaneous (3 U/kg) or intracisternal (0.3 or 1 U/kg) administration of BoNT-A significantly inhibited the formalin-induced nociceptive response in the second phase.These results suggest that the central antinociceptive effects the peripherally or centrally administered BoNT-A are mediated by transcytosed BoNT-A or direct inhibition of trigeminal neurons.Our data suggest that central targets of BoNT-A might provide a new therapeutic tool for the treatment of orofacial chronic pain conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.

ABSTRACT
We examined the effects of peripherally or centrally administered botulinum neurotoxin type A (BoNT-A) on orofacial inflammatory pain to evaluate the antinociceptive effect of BoNT-A and its underlying mechanisms. The experiments were carried out on male Sprague-Dawley rats. Subcutaneous (3 U/kg) or intracisternal (0.3 or 1 U/kg) administration of BoNT-A significantly inhibited the formalin-induced nociceptive response in the second phase. Both subcutaneous (1 or 3 U/kg) and intracisternal (0.3 or 1 U/kg) injection of BoNT-A increased the latency of head withdrawal response in the complete Freund's adjuvant (CFA)-treated rats. Intracisternal administration of N-methyl-D-aspartate (NMDA) evoked nociceptive behavior via the activation of trigeminal neurons, which was attenuated by the subcutaneous or intracisternal injection of BoNT-A. Intracisternal injection of NMDA up-regulated c-Fos expression in the trigeminal neurons of the medullary dorsal horn. Subcutaneous (3 U/kg) or intracisternal (1 U/kg) administration of BoNT-A significantly reduced the number of c-Fos immunoreactive neurons in the NMDA-treated rats. These results suggest that the central antinociceptive effects the peripherally or centrally administered BoNT-A are mediated by transcytosed BoNT-A or direct inhibition of trigeminal neurons. Our data suggest that central targets of BoNT-A might provide a new therapeutic tool for the treatment of orofacial chronic pain conditions.

No MeSH data available.


Related in: MedlinePlus