Vagotomy accelerates the onset of symptoms during early disease progression and worsens joint-level pathogenesis in a male rat model of chronic knee osteoarthritis

Objective: Low vagal tone is common in osteoarthritis (OA) comorbidities and results in greater peripheral inflammation. Characterizing vagal tone's role in OA pathogenesis may offer insights into OA's influences beyond the articular joint. We hypothesized that low vagal tone would acceler...

Full description

Bibliographic Details
Main Authors: Carlos J. Cruz, Taylor D. Yeater, Jacob L. Griffith, Kyle D. Allen
Format: Article
Language:English
Published: Elsevier 2024-06-01
Series:Osteoarthritis and Cartilage Open
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2665913124000347
_version_ 1797202961231773696
author Carlos J. Cruz
Taylor D. Yeater
Jacob L. Griffith
Kyle D. Allen
author_facet Carlos J. Cruz
Taylor D. Yeater
Jacob L. Griffith
Kyle D. Allen
author_sort Carlos J. Cruz
collection DOAJ
description Objective: Low vagal tone is common in osteoarthritis (OA) comorbidities and results in greater peripheral inflammation. Characterizing vagal tone's role in OA pathogenesis may offer insights into OA's influences beyond the articular joint. We hypothesized that low vagal tone would accelerate onset of OA-related gait changes and worsen joint damage in a rat knee OA model. Methods: Knee OA was induced in male Sprague Dawley rats by transecting the medial collateral ligament and medial meniscus. Then, left cervical vagus nerve transection (VGX, n ​= ​9) or sham VGX (non-VGX, n ​= ​6) was performed. Gait and tactile sensitivity were assessed at baseline and across 12 weeks, with histology and systemic inflammation evaluated at endpoint. Results: At week 4, VGX animals showed limping gait characteristics through shifted stance times from their OA to non-OA limb (p ​= ​0.055; stance time imbalance ​= ​1.6 ​± ​1.6%) and shifted foot strike locations (p ​< ​0.001; spatial symmetry ​= ​48.4 ​± ​0.835%), while non-VGX animals walked with a balanced and symmetric gait. Also at week 4, while VGX animals had a mechanical sensitivity (50% withdrawal threshold) of 13.97 ​± ​7.70 compared to the non-VGX animal sensitivity of 29.74 ​± ​9.43, this difference was not statistically significant. Histologically, VGX animals showed thinner tibial cartilage and greater subchondral bone area than non-VGX animals (p ​= ​0.076; VGX: 0.80 ​± ​0.036 ​mm2; non-VGX: 0.736 ​± ​0.066 ​mm2). No group differences in systemic inflammation were observed at endpoint. Conclusions: VGX resulted in quicker onset of OA-related symptoms but remained unchanged at later timepoints. VGX also had thinner cartilage and abnormal bone remodeling than non-VGX. Overall, low vagal tone had mild effects on OA symptoms and joint remodeling, and not at the level seen in common OA comorbidities.
first_indexed 2024-04-24T08:11:45Z
format Article
id doaj.art-6a834e635df843ae91d53d39eef537b7
institution Directory Open Access Journal
issn 2665-9131
language English
last_indexed 2024-04-24T08:11:45Z
publishDate 2024-06-01
publisher Elsevier
record_format Article
series Osteoarthritis and Cartilage Open
spelling doaj.art-6a834e635df843ae91d53d39eef537b72024-04-17T04:49:51ZengElsevierOsteoarthritis and Cartilage Open2665-91312024-06-0162100467Vagotomy accelerates the onset of symptoms during early disease progression and worsens joint-level pathogenesis in a male rat model of chronic knee osteoarthritisCarlos J. Cruz0Taylor D. Yeater1Jacob L. Griffith2Kyle D. Allen3J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA; Pain Research and Intervention Center of Excellence, University of Florida, Gainesville, FL, USAJ. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA; Pain Research and Intervention Center of Excellence, University of Florida, Gainesville, FL, USAJ. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA; Pain Research and Intervention Center of Excellence, University of Florida, Gainesville, FL, USAJ. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA; Department of Orthopaedic Surgery and Sports Medicine, College of Medicine, University of Florida, Gainesville, FL, USA; Pain Research and Intervention Center of Excellence, University of Florida, Gainesville, FL, USA; Corresponding author. Professor, J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, 1275 Center Drive, Biomedical Sciences Building, Gainesville, FL 32610, USA.Objective: Low vagal tone is common in osteoarthritis (OA) comorbidities and results in greater peripheral inflammation. Characterizing vagal tone's role in OA pathogenesis may offer insights into OA's influences beyond the articular joint. We hypothesized that low vagal tone would accelerate onset of OA-related gait changes and worsen joint damage in a rat knee OA model. Methods: Knee OA was induced in male Sprague Dawley rats by transecting the medial collateral ligament and medial meniscus. Then, left cervical vagus nerve transection (VGX, n ​= ​9) or sham VGX (non-VGX, n ​= ​6) was performed. Gait and tactile sensitivity were assessed at baseline and across 12 weeks, with histology and systemic inflammation evaluated at endpoint. Results: At week 4, VGX animals showed limping gait characteristics through shifted stance times from their OA to non-OA limb (p ​= ​0.055; stance time imbalance ​= ​1.6 ​± ​1.6%) and shifted foot strike locations (p ​< ​0.001; spatial symmetry ​= ​48.4 ​± ​0.835%), while non-VGX animals walked with a balanced and symmetric gait. Also at week 4, while VGX animals had a mechanical sensitivity (50% withdrawal threshold) of 13.97 ​± ​7.70 compared to the non-VGX animal sensitivity of 29.74 ​± ​9.43, this difference was not statistically significant. Histologically, VGX animals showed thinner tibial cartilage and greater subchondral bone area than non-VGX animals (p ​= ​0.076; VGX: 0.80 ​± ​0.036 ​mm2; non-VGX: 0.736 ​± ​0.066 ​mm2). No group differences in systemic inflammation were observed at endpoint. Conclusions: VGX resulted in quicker onset of OA-related symptoms but remained unchanged at later timepoints. VGX also had thinner cartilage and abnormal bone remodeling than non-VGX. Overall, low vagal tone had mild effects on OA symptoms and joint remodeling, and not at the level seen in common OA comorbidities.http://www.sciencedirect.com/science/article/pii/S2665913124000347OsteoarthritisAutonomic nervous systemVagotomyBrain-joint axisRat model
spellingShingle Carlos J. Cruz
Taylor D. Yeater
Jacob L. Griffith
Kyle D. Allen
Vagotomy accelerates the onset of symptoms during early disease progression and worsens joint-level pathogenesis in a male rat model of chronic knee osteoarthritis
Osteoarthritis and Cartilage Open
Osteoarthritis
Autonomic nervous system
Vagotomy
Brain-joint axis
Rat model
title Vagotomy accelerates the onset of symptoms during early disease progression and worsens joint-level pathogenesis in a male rat model of chronic knee osteoarthritis
title_full Vagotomy accelerates the onset of symptoms during early disease progression and worsens joint-level pathogenesis in a male rat model of chronic knee osteoarthritis
title_fullStr Vagotomy accelerates the onset of symptoms during early disease progression and worsens joint-level pathogenesis in a male rat model of chronic knee osteoarthritis
title_full_unstemmed Vagotomy accelerates the onset of symptoms during early disease progression and worsens joint-level pathogenesis in a male rat model of chronic knee osteoarthritis
title_short Vagotomy accelerates the onset of symptoms during early disease progression and worsens joint-level pathogenesis in a male rat model of chronic knee osteoarthritis
title_sort vagotomy accelerates the onset of symptoms during early disease progression and worsens joint level pathogenesis in a male rat model of chronic knee osteoarthritis
topic Osteoarthritis
Autonomic nervous system
Vagotomy
Brain-joint axis
Rat model
url http://www.sciencedirect.com/science/article/pii/S2665913124000347
work_keys_str_mv AT carlosjcruz vagotomyacceleratestheonsetofsymptomsduringearlydiseaseprogressionandworsensjointlevelpathogenesisinamaleratmodelofchronickneeosteoarthritis
AT taylordyeater vagotomyacceleratestheonsetofsymptomsduringearlydiseaseprogressionandworsensjointlevelpathogenesisinamaleratmodelofchronickneeosteoarthritis
AT jacoblgriffith vagotomyacceleratestheonsetofsymptomsduringearlydiseaseprogressionandworsensjointlevelpathogenesisinamaleratmodelofchronickneeosteoarthritis
AT kyledallen vagotomyacceleratestheonsetofsymptomsduringearlydiseaseprogressionandworsensjointlevelpathogenesisinamaleratmodelofchronickneeosteoarthritis