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Comparative Assessment of the Activity of Racemic and Dextrorotatory Forms of Thioctic (Alpha-Lipoic) Acid in Low Back Pain: Preclinical Results and Clinical Evidences From an Open Randomized Trial

Peripheral neuropathies, characterized by altered nociceptive and muscular functions, are related to oxidative stress. Thioctic acid is a natural antioxidant existing as two optical isomers, but most clinically used as racemic mixture. The present study investigated the central nervous system’s chan...

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Autores principales: Pacini, Alessandra, Tomassoni, Daniele, Trallori, Elena, Micheli, Laura, Amenta, Francesco, Ghelardini, Carla, Di Cesare Mannelli, Lorenzo, Traini, Enea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959756/
https://www.ncbi.nlm.nih.gov/pubmed/33732153
http://dx.doi.org/10.3389/fphar.2021.607572
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author Pacini, Alessandra
Tomassoni, Daniele
Trallori, Elena
Micheli, Laura
Amenta, Francesco
Ghelardini, Carla
Di Cesare Mannelli, Lorenzo
Traini, Enea
author_facet Pacini, Alessandra
Tomassoni, Daniele
Trallori, Elena
Micheli, Laura
Amenta, Francesco
Ghelardini, Carla
Di Cesare Mannelli, Lorenzo
Traini, Enea
author_sort Pacini, Alessandra
collection PubMed
description Peripheral neuropathies, characterized by altered nociceptive and muscular functions, are related to oxidative stress. Thioctic acid is a natural antioxidant existing as two optical isomers, but most clinically used as racemic mixture. The present study investigated the central nervous system’s changes which followed loose-ligation-derived compression of sciatic nerve, the putative neuroprotective role of thioctic acid and the pain-alleviating effect on low-back pain suffering patients. Loose ligation of the right sciatic nerve was performed in spontaneously hypertensive rats (SHR), a model of increased oxidative stress, and in normotensive Wistar-Kyoto rats (WKY). Animals with sciatic nerve ligation were left untreated or were treated intraperitoneally for 15 days with 250 μmol·kg(−1)·die(−1) of (+/−)-thioctic acid; 125 μmol·kg(−1)·die(−1) of (+/−)-thioctic acid; 125 μmol·kg(−1)·die(−1) of (+)-thioctic acid lysine salt; 125 μmol·kg(−1)·die(−1) of (−)-thioctic acid; 300 μmol·kg(−1)·die(−1) pregabalin. Control SHR and WKY rats received the same amounts of vehicle. The clinical trial NESTIORADE (Sensory-Motor Neuropathies of the Sciatic Nerve: Comparative evaluation of the effect of racemic and dextro-rotatory forms of thioctic acid) examined 100 patients (49 males and 51 females aged 53 ± 11 years) dividing them into two equal-numbered groups, each treated daily for 60 days with 600 mg of (+/−)-thioctic acid or (+)-thioctic acid, respectively. The trial was registered prior to patient enrollment at EudraCT website (OSSC Number: 2011-000964-81). In the preclinical study, (+)-thioctic acid was more active than (+/−)- or (−)-enantiomers in relieving pain and protecting peripheral nerve as well as in reducing oxidative stress and astrogliosis in the spinal cord. Main findings of NESTIORADE clinical trial showed a greater influence on painful symptomatology, a quicker recovery and a better impact on quality of life of (+)-thioctic acid vs. (+/−)-thioctic acid. These data may have a pharmacological and pharmacoeconomical relevance and suggest that thioctic acid, above all (+)-enantiomer, could be considered for treatment of low-back pain involving neuropathy.
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spelling pubmed-79597562021-03-16 Comparative Assessment of the Activity of Racemic and Dextrorotatory Forms of Thioctic (Alpha-Lipoic) Acid in Low Back Pain: Preclinical Results and Clinical Evidences From an Open Randomized Trial Pacini, Alessandra Tomassoni, Daniele Trallori, Elena Micheli, Laura Amenta, Francesco Ghelardini, Carla Di Cesare Mannelli, Lorenzo Traini, Enea Front Pharmacol Pharmacology Peripheral neuropathies, characterized by altered nociceptive and muscular functions, are related to oxidative stress. Thioctic acid is a natural antioxidant existing as two optical isomers, but most clinically used as racemic mixture. The present study investigated the central nervous system’s changes which followed loose-ligation-derived compression of sciatic nerve, the putative neuroprotective role of thioctic acid and the pain-alleviating effect on low-back pain suffering patients. Loose ligation of the right sciatic nerve was performed in spontaneously hypertensive rats (SHR), a model of increased oxidative stress, and in normotensive Wistar-Kyoto rats (WKY). Animals with sciatic nerve ligation were left untreated or were treated intraperitoneally for 15 days with 250 μmol·kg(−1)·die(−1) of (+/−)-thioctic acid; 125 μmol·kg(−1)·die(−1) of (+/−)-thioctic acid; 125 μmol·kg(−1)·die(−1) of (+)-thioctic acid lysine salt; 125 μmol·kg(−1)·die(−1) of (−)-thioctic acid; 300 μmol·kg(−1)·die(−1) pregabalin. Control SHR and WKY rats received the same amounts of vehicle. The clinical trial NESTIORADE (Sensory-Motor Neuropathies of the Sciatic Nerve: Comparative evaluation of the effect of racemic and dextro-rotatory forms of thioctic acid) examined 100 patients (49 males and 51 females aged 53 ± 11 years) dividing them into two equal-numbered groups, each treated daily for 60 days with 600 mg of (+/−)-thioctic acid or (+)-thioctic acid, respectively. The trial was registered prior to patient enrollment at EudraCT website (OSSC Number: 2011-000964-81). In the preclinical study, (+)-thioctic acid was more active than (+/−)- or (−)-enantiomers in relieving pain and protecting peripheral nerve as well as in reducing oxidative stress and astrogliosis in the spinal cord. Main findings of NESTIORADE clinical trial showed a greater influence on painful symptomatology, a quicker recovery and a better impact on quality of life of (+)-thioctic acid vs. (+/−)-thioctic acid. These data may have a pharmacological and pharmacoeconomical relevance and suggest that thioctic acid, above all (+)-enantiomer, could be considered for treatment of low-back pain involving neuropathy. Frontiers Media S.A. 2021-02-24 /pmc/articles/PMC7959756/ /pubmed/33732153 http://dx.doi.org/10.3389/fphar.2021.607572 Text en Copyright © 2021 Pacini, Tomassoni, Trallori, Micheli, Amenta, Ghelardini, Di Cesare Mannelli and Traini. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (http://creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Pacini, Alessandra
Tomassoni, Daniele
Trallori, Elena
Micheli, Laura
Amenta, Francesco
Ghelardini, Carla
Di Cesare Mannelli, Lorenzo
Traini, Enea
Comparative Assessment of the Activity of Racemic and Dextrorotatory Forms of Thioctic (Alpha-Lipoic) Acid in Low Back Pain: Preclinical Results and Clinical Evidences From an Open Randomized Trial
title Comparative Assessment of the Activity of Racemic and Dextrorotatory Forms of Thioctic (Alpha-Lipoic) Acid in Low Back Pain: Preclinical Results and Clinical Evidences From an Open Randomized Trial
title_full Comparative Assessment of the Activity of Racemic and Dextrorotatory Forms of Thioctic (Alpha-Lipoic) Acid in Low Back Pain: Preclinical Results and Clinical Evidences From an Open Randomized Trial
title_fullStr Comparative Assessment of the Activity of Racemic and Dextrorotatory Forms of Thioctic (Alpha-Lipoic) Acid in Low Back Pain: Preclinical Results and Clinical Evidences From an Open Randomized Trial
title_full_unstemmed Comparative Assessment of the Activity of Racemic and Dextrorotatory Forms of Thioctic (Alpha-Lipoic) Acid in Low Back Pain: Preclinical Results and Clinical Evidences From an Open Randomized Trial
title_short Comparative Assessment of the Activity of Racemic and Dextrorotatory Forms of Thioctic (Alpha-Lipoic) Acid in Low Back Pain: Preclinical Results and Clinical Evidences From an Open Randomized Trial
title_sort comparative assessment of the activity of racemic and dextrorotatory forms of thioctic (alpha-lipoic) acid in low back pain: preclinical results and clinical evidences from an open randomized trial
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959756/
https://www.ncbi.nlm.nih.gov/pubmed/33732153
http://dx.doi.org/10.3389/fphar.2021.607572
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