Spinal cord injury in mice affects central and peripheral pathology in a severity-dependent manner.


Journal

Pain
ISSN: 1872-6623
Titre abrégé: Pain
Pays: United States
ID NLM: 7508686

Informations de publication

Date de publication:
01 06 2022
Historique:
received: 30 04 2021
accepted: 25 08 2021
pubmed: 8 9 2021
medline: 18 5 2022
entrez: 7 9 2021
Statut: ppublish

Résumé

Chronic pain is a common medical complication experienced by those living with spinal cord injury (SCI) and leads to worsened quality of life. The pathophysiology of SCI pain is poorly understood, hampering the development of safe and efficacious therapeutics. We therefore sought to develop a clinically relevant model of SCI with a strong pain phenotype and characterize the central and peripheral pathology after injury. A contusion (50 kdyn) injury, with and without sustained compression (60 seconds) of the spinal cord, was performed on female C57BL/6J mice. Mice with compression of the spinal cord exhibited significantly greater heat and mechanical hypersensitivity starting at 7 days postinjury, concomitant with reduced locomotor function, compared with those without compression. Immunohistochemical analysis of spinal cord tissue revealed significantly less myelin sparing and increased macrophage activation in mice with compression compared with those without. As measured by flow cytometry, immune cell infiltration and activation were significantly greater in the spinal cord (phagocytic myeloid cells and microglia) and dorsal root ganglia (Ly6C+ monocytes) after compression injury. We also decided to investigate the gastrointestinal microbiome, as it has been shown to be altered in patients with SCI and has recently been shown to play a role in immune system maturation and pain. We found increased dysbiosis of the gastrointestinal microbiome in an injury severity-dependent manner. The use of this contusion-compression model of SCI may help advance the preclinical assessment of acute and chronic SCI pain and lead to a better understanding of mechanisms contributing to this pain.

Identifiants

pubmed: 34490852
doi: 10.1097/j.pain.0000000000002471
pii: 00006396-202206000-00021
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1172-1185

Subventions

Organisme : CIHR
ID : SCA-145102
Pays : Canada

Informations de copyright

Copyright © 2021 International Association for the Study of Pain.

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Auteurs

Courtney A Bannerman (CA)

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.

Katya Douchant (K)

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
Division of Microbiology, Kingston Health Sciences Centre, Kingston, ON, Canada.

Julia P Segal (JP)

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.

Mitra Knezic (M)

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.

Alexandra E Mack (AE)

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.

Caitlin Lundell-Creagh (C)

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.

Jaqueline R Silva (JR)

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
Department of Anesthesiology and Perioperative Medicine, Queen's University, Kingston, ON, Canada.
Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.

Scott Duggan (S)

Department of Anesthesiology and Perioperative Medicine, Queen's University, Kingston, ON, Canada.

Prameet Sheth (P)

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
Division of Microbiology, Kingston Health Sciences Centre, Kingston, ON, Canada.
Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Gastrointestinal Diseases Research Unit, Kingston Health Sciences Centre, Kingston, ON, Canada.

Nader Ghasemlou (N)

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
Department of Anesthesiology and Perioperative Medicine, Queen's University, Kingston, ON, Canada.
Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.

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