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Effect of Tetrodotoxin Pellets in a Rat Model of Postherpetic Neuralgia
Postherpetic neuralgia (PHN) is nerve pain caused by a reactivation of the varicella zoster virus. Medications are used to reduce PHN but their use is limited by serious side effects. Tetrodotoxin (TTX) is a latent neurotoxin that can block neuropathic pain, but its therapeutic index is only 3–5 tim...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6025269/ https://www.ncbi.nlm.nih.gov/pubmed/29874779 http://dx.doi.org/10.3390/md16060195 |
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author | Hong, Bihong Sun, Jipeng Zheng, Hongzhi Le, Qingqing Wang, Changsen Bai, Kaikai He, Jianlin He, Huanghuang Dong, Yanming |
author_facet | Hong, Bihong Sun, Jipeng Zheng, Hongzhi Le, Qingqing Wang, Changsen Bai, Kaikai He, Jianlin He, Huanghuang Dong, Yanming |
author_sort | Hong, Bihong |
collection | PubMed |
description | Postherpetic neuralgia (PHN) is nerve pain caused by a reactivation of the varicella zoster virus. Medications are used to reduce PHN but their use is limited by serious side effects. Tetrodotoxin (TTX) is a latent neurotoxin that can block neuropathic pain, but its therapeutic index is only 3–5 times with intravenous or intramuscular injection. Therefore, we prepared oral TTX pellets and examined their effect in a rat model of PHN induced by resiniferatoxin (RTX). Oral TTX pellets were significantly effective at preventing RTX-induced mechanical and thermal allodynia, and similar to pregabalin. Moreover, oral administration of TTX pellets dose-dependently inhibited RTX-induced PHN compared with intramuscular administration of TTX injection. We also studied the pharmacokinetic profile of TTX pellets. Our results showed that the blood concentration of TTX reached a maximum plasma concentration (C(max)) at around 2 h, with an elimination half-life time (t(1/2)) of 3.23 ± 1.74 h after intragastric administration. The median lethal dose (LD(50)) of TTX pellets was 517.43 μg/kg via oral administration to rats, while the median effective dose (ED50) was approximately 5.85 μg/kg, and the therapeutic index was 88.45. Altogether, this has indicated that oral TTX pellets greatly enhance safety when compared with TTX injection. |
format | Online Article Text |
id | pubmed-6025269 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-60252692018-07-09 Effect of Tetrodotoxin Pellets in a Rat Model of Postherpetic Neuralgia Hong, Bihong Sun, Jipeng Zheng, Hongzhi Le, Qingqing Wang, Changsen Bai, Kaikai He, Jianlin He, Huanghuang Dong, Yanming Mar Drugs Article Postherpetic neuralgia (PHN) is nerve pain caused by a reactivation of the varicella zoster virus. Medications are used to reduce PHN but their use is limited by serious side effects. Tetrodotoxin (TTX) is a latent neurotoxin that can block neuropathic pain, but its therapeutic index is only 3–5 times with intravenous or intramuscular injection. Therefore, we prepared oral TTX pellets and examined their effect in a rat model of PHN induced by resiniferatoxin (RTX). Oral TTX pellets were significantly effective at preventing RTX-induced mechanical and thermal allodynia, and similar to pregabalin. Moreover, oral administration of TTX pellets dose-dependently inhibited RTX-induced PHN compared with intramuscular administration of TTX injection. We also studied the pharmacokinetic profile of TTX pellets. Our results showed that the blood concentration of TTX reached a maximum plasma concentration (C(max)) at around 2 h, with an elimination half-life time (t(1/2)) of 3.23 ± 1.74 h after intragastric administration. The median lethal dose (LD(50)) of TTX pellets was 517.43 μg/kg via oral administration to rats, while the median effective dose (ED50) was approximately 5.85 μg/kg, and the therapeutic index was 88.45. Altogether, this has indicated that oral TTX pellets greatly enhance safety when compared with TTX injection. MDPI 2018-06-05 /pmc/articles/PMC6025269/ /pubmed/29874779 http://dx.doi.org/10.3390/md16060195 Text en © 2018 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hong, Bihong Sun, Jipeng Zheng, Hongzhi Le, Qingqing Wang, Changsen Bai, Kaikai He, Jianlin He, Huanghuang Dong, Yanming Effect of Tetrodotoxin Pellets in a Rat Model of Postherpetic Neuralgia |
title | Effect of Tetrodotoxin Pellets in a Rat Model of Postherpetic Neuralgia |
title_full | Effect of Tetrodotoxin Pellets in a Rat Model of Postherpetic Neuralgia |
title_fullStr | Effect of Tetrodotoxin Pellets in a Rat Model of Postherpetic Neuralgia |
title_full_unstemmed | Effect of Tetrodotoxin Pellets in a Rat Model of Postherpetic Neuralgia |
title_short | Effect of Tetrodotoxin Pellets in a Rat Model of Postherpetic Neuralgia |
title_sort | effect of tetrodotoxin pellets in a rat model of postherpetic neuralgia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6025269/ https://www.ncbi.nlm.nih.gov/pubmed/29874779 http://dx.doi.org/10.3390/md16060195 |
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