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Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model

Systemic injection of a nerve growth factor (NGF) antibody has been proven to have a significant relevance in relieving osteoarthritis (OA) pain, while its adverse effects remain a safety concern for patients. A local low-dose injection is thought to minimize adverse effects. In this study, OA was i...

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Autores principales: Tian, Yuan, Onodera, Tomohiro, Terkawi, Mohamad Alaa, Iwasaki, Koji, Hishimura, Ryosuke, Liang, Dawei, Miyazaki, Takuji, Iwasaki, Norimasa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962042/
https://www.ncbi.nlm.nih.gov/pubmed/33806315
http://dx.doi.org/10.3390/ijms22052552
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author Tian, Yuan
Onodera, Tomohiro
Terkawi, Mohamad Alaa
Iwasaki, Koji
Hishimura, Ryosuke
Liang, Dawei
Miyazaki, Takuji
Iwasaki, Norimasa
author_facet Tian, Yuan
Onodera, Tomohiro
Terkawi, Mohamad Alaa
Iwasaki, Koji
Hishimura, Ryosuke
Liang, Dawei
Miyazaki, Takuji
Iwasaki, Norimasa
author_sort Tian, Yuan
collection PubMed
description Systemic injection of a nerve growth factor (NGF) antibody has been proven to have a significant relevance in relieving osteoarthritis (OA) pain, while its adverse effects remain a safety concern for patients. A local low-dose injection is thought to minimize adverse effects. In this study, OA was induced in an 8-week-old male Sprague–Dawley (SD) rat joint by monoiodoacetate (MIA) injection for 2 weeks, and the effect of weekly injections of low-dose (1, 10, and 100 µg) NGF antibody or saline (control) was evaluated. Behavioral tests were performed, and at the end of week 6, all rats were sacrificed and their knee joints were collected for macroscopic and histological evaluations. Results showed that 100 µg NGF antibody injection relieved pain in OA rats, as evidenced from improved weight-bearing performance but not allodynia. In contrast, no significant differences were observed in macroscopic and histological scores between rats from different groups, demonstrating that intra-articular treatment does not worsen OA progression. These results suggest that local administration yielded a low effective NGF antibody dose that may serve as an alternative approach to systemic injection for the treatment of patients with OA.
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spelling pubmed-79620422021-03-17 Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model Tian, Yuan Onodera, Tomohiro Terkawi, Mohamad Alaa Iwasaki, Koji Hishimura, Ryosuke Liang, Dawei Miyazaki, Takuji Iwasaki, Norimasa Int J Mol Sci Article Systemic injection of a nerve growth factor (NGF) antibody has been proven to have a significant relevance in relieving osteoarthritis (OA) pain, while its adverse effects remain a safety concern for patients. A local low-dose injection is thought to minimize adverse effects. In this study, OA was induced in an 8-week-old male Sprague–Dawley (SD) rat joint by monoiodoacetate (MIA) injection for 2 weeks, and the effect of weekly injections of low-dose (1, 10, and 100 µg) NGF antibody or saline (control) was evaluated. Behavioral tests were performed, and at the end of week 6, all rats were sacrificed and their knee joints were collected for macroscopic and histological evaluations. Results showed that 100 µg NGF antibody injection relieved pain in OA rats, as evidenced from improved weight-bearing performance but not allodynia. In contrast, no significant differences were observed in macroscopic and histological scores between rats from different groups, demonstrating that intra-articular treatment does not worsen OA progression. These results suggest that local administration yielded a low effective NGF antibody dose that may serve as an alternative approach to systemic injection for the treatment of patients with OA. MDPI 2021-03-04 /pmc/articles/PMC7962042/ /pubmed/33806315 http://dx.doi.org/10.3390/ijms22052552 Text en © 2021 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
Tian, Yuan
Onodera, Tomohiro
Terkawi, Mohamad Alaa
Iwasaki, Koji
Hishimura, Ryosuke
Liang, Dawei
Miyazaki, Takuji
Iwasaki, Norimasa
Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model
title Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model
title_full Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model
title_fullStr Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model
title_full_unstemmed Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model
title_short Local Administration of Low-Dose Nerve Growth Factor Antibody Reduced Pain in a Rat Osteoarthritis Model
title_sort local administration of low-dose nerve growth factor antibody reduced pain in a rat osteoarthritis model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962042/
https://www.ncbi.nlm.nih.gov/pubmed/33806315
http://dx.doi.org/10.3390/ijms22052552
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