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Molecular basis for the dosing time-dependency of anti-allodynic effects of gabapentin in a mouse model of neuropathic pain
BACKGROUND: Neuropathic pain is characterized by hypersensitivity to innocuous stimuli (tactile allodynia) that is nearly always resistant to NSAIDs or even opioids. Gabapentin, a GABA analogue, was originally developed to treat epilepsy. Accumulating clinical evidence supports the effectiveness of...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3009974/ https://www.ncbi.nlm.nih.gov/pubmed/21108841 http://dx.doi.org/10.1186/1744-8069-6-83 |
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author | Kusunose, Naoki Koyanagi, Satoru Hamamura, Kengo Matsunaga, Naoya Yoshida, Miyako Uchida, Takahiro Tsuda, Makoto Inoue, Kazuhide Ohdo, Shigehiro |
author_facet | Kusunose, Naoki Koyanagi, Satoru Hamamura, Kengo Matsunaga, Naoya Yoshida, Miyako Uchida, Takahiro Tsuda, Makoto Inoue, Kazuhide Ohdo, Shigehiro |
author_sort | Kusunose, Naoki |
collection | PubMed |
description | BACKGROUND: Neuropathic pain is characterized by hypersensitivity to innocuous stimuli (tactile allodynia) that is nearly always resistant to NSAIDs or even opioids. Gabapentin, a GABA analogue, was originally developed to treat epilepsy. Accumulating clinical evidence supports the effectiveness of this drug for diverse neuropathic pain. In this study, we showed that the anti-allodynic effect of gabapentin was changed by the circadian oscillation in the expression of its target molecule, the calcium channel α2δ-1 subunit. RESULTS: Mice were underwent partial sciatic nerve ligation (PSL) to create a model of neuropathic pain. The paw withdrawal threshold (PWT) in PSL mice significantly decreased and fluctuated with a period length about 24 h. The PWT in PSL mice was dose-dependently increased by intraperitoneal injection of gabapentin, but the anti-allodynic effects varied according to its dosing time. The protein levels of α2δ-1 subunit were up-regulated in the DRG of PSL mice, but the protein levels oscillated in a circadian time-dependent manner. The time-dependent oscillation of α2δ-1 subunit protein correlated with fluctuations in the maximal binding capacity of gabapentin. The anti-allodynic effect of gabapentin was attenuated at the times of the day when α2δ-1 subunit protein was abundant. CONCLUSIONS: These findings suggest that the dosing time-dependent difference in the anti-allodynic effects of gabapentin is attributable to the circadian oscillation of α2δ-1 subunit expression in the DRG and indicate that the optimizing its dosing schedule helps to achieve rational pharmacotherapy for neuropathic pain. |
format | Text |
id | pubmed-3009974 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-30099742010-12-25 Molecular basis for the dosing time-dependency of anti-allodynic effects of gabapentin in a mouse model of neuropathic pain Kusunose, Naoki Koyanagi, Satoru Hamamura, Kengo Matsunaga, Naoya Yoshida, Miyako Uchida, Takahiro Tsuda, Makoto Inoue, Kazuhide Ohdo, Shigehiro Mol Pain Research BACKGROUND: Neuropathic pain is characterized by hypersensitivity to innocuous stimuli (tactile allodynia) that is nearly always resistant to NSAIDs or even opioids. Gabapentin, a GABA analogue, was originally developed to treat epilepsy. Accumulating clinical evidence supports the effectiveness of this drug for diverse neuropathic pain. In this study, we showed that the anti-allodynic effect of gabapentin was changed by the circadian oscillation in the expression of its target molecule, the calcium channel α2δ-1 subunit. RESULTS: Mice were underwent partial sciatic nerve ligation (PSL) to create a model of neuropathic pain. The paw withdrawal threshold (PWT) in PSL mice significantly decreased and fluctuated with a period length about 24 h. The PWT in PSL mice was dose-dependently increased by intraperitoneal injection of gabapentin, but the anti-allodynic effects varied according to its dosing time. The protein levels of α2δ-1 subunit were up-regulated in the DRG of PSL mice, but the protein levels oscillated in a circadian time-dependent manner. The time-dependent oscillation of α2δ-1 subunit protein correlated with fluctuations in the maximal binding capacity of gabapentin. The anti-allodynic effect of gabapentin was attenuated at the times of the day when α2δ-1 subunit protein was abundant. CONCLUSIONS: These findings suggest that the dosing time-dependent difference in the anti-allodynic effects of gabapentin is attributable to the circadian oscillation of α2δ-1 subunit expression in the DRG and indicate that the optimizing its dosing schedule helps to achieve rational pharmacotherapy for neuropathic pain. BioMed Central 2010-11-26 /pmc/articles/PMC3009974/ /pubmed/21108841 http://dx.doi.org/10.1186/1744-8069-6-83 Text en Copyright ©2010 Kusunose et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<url>http://creativecommons.org/licenses/by/2.0</url>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Kusunose, Naoki Koyanagi, Satoru Hamamura, Kengo Matsunaga, Naoya Yoshida, Miyako Uchida, Takahiro Tsuda, Makoto Inoue, Kazuhide Ohdo, Shigehiro Molecular basis for the dosing time-dependency of anti-allodynic effects of gabapentin in a mouse model of neuropathic pain |
title | Molecular basis for the dosing time-dependency of anti-allodynic effects of gabapentin in a mouse model of neuropathic pain |
title_full | Molecular basis for the dosing time-dependency of anti-allodynic effects of gabapentin in a mouse model of neuropathic pain |
title_fullStr | Molecular basis for the dosing time-dependency of anti-allodynic effects of gabapentin in a mouse model of neuropathic pain |
title_full_unstemmed | Molecular basis for the dosing time-dependency of anti-allodynic effects of gabapentin in a mouse model of neuropathic pain |
title_short | Molecular basis for the dosing time-dependency of anti-allodynic effects of gabapentin in a mouse model of neuropathic pain |
title_sort | molecular basis for the dosing time-dependency of anti-allodynic effects of gabapentin in a mouse model of neuropathic pain |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3009974/ https://www.ncbi.nlm.nih.gov/pubmed/21108841 http://dx.doi.org/10.1186/1744-8069-6-83 |
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