Sertoli cell transplantation attenuates microglial activation and inhibits TRPC6 expression in neuropathic pain induced by spinal cord injury.
Analgesics
Animals
Cell Transplantation
/ adverse effects
Hyperalgesia
/ etiology
Male
Microglia
/ metabolism
Neuralgia
/ etiology
Rats
Rats, Sprague-Dawley
Rats, Wistar
Sertoli Cells
/ metabolism
Spinal Cord
/ pathology
Spinal Cord Injuries
/ complications
TOR Serine-Threonine Kinases
/ metabolism
TRPC Cation Channels
TRPC6 Cation Channel
/ metabolism
Cell transplantation
Neuropathic pain
Sertoli cells
Spinal cord injury
Journal
Physiology & behavior
ISSN: 1873-507X
Titre abrégé: Physiol Behav
Pays: United States
ID NLM: 0151504
Informations de publication
Date de publication:
01 07 2022
01 07 2022
Historique:
received:
14
12
2021
revised:
10
03
2022
accepted:
08
04
2022
pubmed:
16
4
2022
medline:
10
5
2022
entrez:
15
4
2022
Statut:
ppublish
Résumé
Cell therapy is a promising treatment method for relieving neuropathic pain caused by spinal cord injuries (SCI). Sertoli cells (SCs) are an attractive choice given their demonstrated secretion of growth factors and immunosuppressant effect. This study mechanistically characterizes the analgesic effect of SCs transplantation. The clip compression SCI model was carried out on the T12-T13 level in male Wistar rats. One-week post-SCI, SCs were transplanted into the site of injury. Animals underwent Basso, Beattie, and Bresnahan locomotor scoring, mechanical allodynia, and thermal hyperalgesia on a weekly basis for a duration of six weeks. Histological examination of the spinal cord and molecular evaluation of Iba-1, P2Y4, TRPC6, and P-mTOR were performed. SCs survival, measured by anti-Müllerian hormone expression in the spinal cord. Animals that received SCs transplantation showed improvement in motor function recovery and pain relief. Furthermore, a cavity was significantly decreased in the transplanted animals (p = 0.0024), the expression level of TRPC6 and caspase3 and the number of activated microglia decreased compared to the SCI animals, and p-mTOR and P2Y4R expression remarkably increased compared to the SCI group. SCs transplantation produces an analgesic effect which may represent a promising treatment for SCI-induced chronic pain.
Sections du résumé
BACKGROUND
Cell therapy is a promising treatment method for relieving neuropathic pain caused by spinal cord injuries (SCI). Sertoli cells (SCs) are an attractive choice given their demonstrated secretion of growth factors and immunosuppressant effect. This study mechanistically characterizes the analgesic effect of SCs transplantation.
METHODS
The clip compression SCI model was carried out on the T12-T13 level in male Wistar rats. One-week post-SCI, SCs were transplanted into the site of injury. Animals underwent Basso, Beattie, and Bresnahan locomotor scoring, mechanical allodynia, and thermal hyperalgesia on a weekly basis for a duration of six weeks. Histological examination of the spinal cord and molecular evaluation of Iba-1, P2Y4, TRPC6, and P-mTOR were performed. SCs survival, measured by anti-Müllerian hormone expression in the spinal cord.
RESULTS
Animals that received SCs transplantation showed improvement in motor function recovery and pain relief. Furthermore, a cavity was significantly decreased in the transplanted animals (p = 0.0024), the expression level of TRPC6 and caspase3 and the number of activated microglia decreased compared to the SCI animals, and p-mTOR and P2Y4R expression remarkably increased compared to the SCI group.
CONCLUSION
SCs transplantation produces an analgesic effect which may represent a promising treatment for SCI-induced chronic pain.
Identifiants
pubmed: 35427673
pii: S0031-9384(22)00113-5
doi: 10.1016/j.physbeh.2022.113807
pii:
doi:
Substances chimiques
Analgesics
0
TRPC Cation Channels
0
TRPC6 Cation Channel
0
Trpc6 protein, rat
0
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
113807Informations de copyright
Copyright © 2022. Published by Elsevier Inc.