Pilot comparison of outcome measures across chemical and surgical experimental models of chronic osteoarthritis in the rat (Rattus norvegicus).

Relatively little work has evaluated both the disease of osteoarthritis (OA) and clinically-relevant pain outcome measures across different OA models in rats. The objective of this study was to compare sensitivity, pain, and histological disease severity across chemical and surgical models of OA in...

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Main Authors: Morika D Williams, Rachel C Meyers, Lauryn A Braxton, Brian Diekman, B Duncan X Lascelles
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0277943
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author Morika D Williams
Rachel C Meyers
Lauryn A Braxton
Brian Diekman
B Duncan X Lascelles
author_facet Morika D Williams
Rachel C Meyers
Lauryn A Braxton
Brian Diekman
B Duncan X Lascelles
author_sort Morika D Williams
collection DOAJ
description Relatively little work has evaluated both the disease of osteoarthritis (OA) and clinically-relevant pain outcome measures across different OA models in rats. The objective of this study was to compare sensitivity, pain, and histological disease severity across chemical and surgical models of OA in the rat. Stifle OA was induced in Sprague-Dawley rats via intraarticular injection of monoiodoacetate (MIA) or surgical transection of anterior cruciate ligament and/or destabilization of medial meniscus (ACL+DMM or DMM alone). Reflexive (e.g., mechanical and thermal stimuli) measures of sensitivity and non-reflexive assays (e.g., lameness, static hindlimb weight-bearing asymmetry, dynamic gait analysis) of pain were measured over time. Joint degeneration was assessed histologically. Six-weeks post OA-induction, the ACL+DMM animals had significantly greater visually observed lameness than MIA animals; however, both ACL+DMM and MIA animals showed equal pain as measured by limb use during ambulation and standing. The MIA animals showed increased thermal, but not mechanical, sensitivity compared to ACL+DMM animals. Joint degeneration was significantly more severe in the MIA model at 6 weeks. Our pilot data suggest both the ACL+DMM and MIA models are equal in terms of clinically relevant pain behaviors, but the MIA model is associated with more severe histological changes over time potentially making it more suitable for screening disease modifying agents. Future work should further characterize each model in terms of complex pain behaviors and biochemical, molecular, and imaging analysis of the sensory system and joint tissues, which will allow for more informed decisions associated with model selection and investigative outcomes.
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spelling doaj.art-ac5f1882189b4edcb7ca489d6342e3692023-01-08T05:31:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-011711e027794310.1371/journal.pone.0277943Pilot comparison of outcome measures across chemical and surgical experimental models of chronic osteoarthritis in the rat (Rattus norvegicus).Morika D WilliamsRachel C MeyersLauryn A BraxtonBrian DiekmanB Duncan X LascellesRelatively little work has evaluated both the disease of osteoarthritis (OA) and clinically-relevant pain outcome measures across different OA models in rats. The objective of this study was to compare sensitivity, pain, and histological disease severity across chemical and surgical models of OA in the rat. Stifle OA was induced in Sprague-Dawley rats via intraarticular injection of monoiodoacetate (MIA) or surgical transection of anterior cruciate ligament and/or destabilization of medial meniscus (ACL+DMM or DMM alone). Reflexive (e.g., mechanical and thermal stimuli) measures of sensitivity and non-reflexive assays (e.g., lameness, static hindlimb weight-bearing asymmetry, dynamic gait analysis) of pain were measured over time. Joint degeneration was assessed histologically. Six-weeks post OA-induction, the ACL+DMM animals had significantly greater visually observed lameness than MIA animals; however, both ACL+DMM and MIA animals showed equal pain as measured by limb use during ambulation and standing. The MIA animals showed increased thermal, but not mechanical, sensitivity compared to ACL+DMM animals. Joint degeneration was significantly more severe in the MIA model at 6 weeks. Our pilot data suggest both the ACL+DMM and MIA models are equal in terms of clinically relevant pain behaviors, but the MIA model is associated with more severe histological changes over time potentially making it more suitable for screening disease modifying agents. Future work should further characterize each model in terms of complex pain behaviors and biochemical, molecular, and imaging analysis of the sensory system and joint tissues, which will allow for more informed decisions associated with model selection and investigative outcomes.https://doi.org/10.1371/journal.pone.0277943
spellingShingle Morika D Williams
Rachel C Meyers
Lauryn A Braxton
Brian Diekman
B Duncan X Lascelles
Pilot comparison of outcome measures across chemical and surgical experimental models of chronic osteoarthritis in the rat (Rattus norvegicus).
PLoS ONE
title Pilot comparison of outcome measures across chemical and surgical experimental models of chronic osteoarthritis in the rat (Rattus norvegicus).
title_full Pilot comparison of outcome measures across chemical and surgical experimental models of chronic osteoarthritis in the rat (Rattus norvegicus).
title_fullStr Pilot comparison of outcome measures across chemical and surgical experimental models of chronic osteoarthritis in the rat (Rattus norvegicus).
title_full_unstemmed Pilot comparison of outcome measures across chemical and surgical experimental models of chronic osteoarthritis in the rat (Rattus norvegicus).
title_short Pilot comparison of outcome measures across chemical and surgical experimental models of chronic osteoarthritis in the rat (Rattus norvegicus).
title_sort pilot comparison of outcome measures across chemical and surgical experimental models of chronic osteoarthritis in the rat rattus norvegicus
url https://doi.org/10.1371/journal.pone.0277943
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