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Bone mesenchymal stem cells attenuate resiniferatoxin-induced neuralgia via inhibiting TRPA1-PKCδ-P38/MAPK-p-P65 pathway in mice.
- Source :
-
Brain research bulletin [Brain Res Bull] 2021 Sep; Vol. 174, pp. 92-102. Date of Electronic Publication: 2021 Jun 04. - Publication Year :
- 2021
-
Abstract
- Treatment of neuropathic pain (NP) resulting from nerve injury is one of the most complicated and challenging in modern practice. Pharmacological treatments for NP are not fully effectively and novel approaches are requisite. Recently, transplantation of bone mesenchymal stem cells (BMSCs) has represented a promising approach for pain relief and neural repair, but how it produces beneficial effects on resiniferatoxin (RTX) induced nerve injury is still unclear. Here, we identified the BMSCs' analgesic effects and their potential mechanisms of microglial cells activation on RTX induced neuralgia. Immunostaining, biochemical studies demonstrated that microglia rather than astrocyte cells activation involved in RTX induced mechanical hyperalgesia, whereas the GFP-labeled BMSCs alleviated this mechanical hyperalgesia. Moreover, pain-related TRPA1, PKCδ, CaMKIIɑ (Calcium/calmodulin dependent protein kinase II), P38/MAPK (mitogen-activated protein kinase), p-P65 activation and expression in the spinal cord were significantly inhibited after BMSC administration. In addition, BMSCs treated RTX mice displayed a lower density of mushroom dendritic spines. Our research suggested that activation of PKCδ-CaMKIIɑ-P38/MAPK-p-P65 pathway and mushroom dendritic spines abnormal increase in the spinal cord is the main mechanism of RTX induced neuropathic pain, and transplant of BMSCs to the damaged nerve may offer promising approach for neuropathic pain.<br /> (Copyright © 2021. Published by Elsevier Inc.)
- Subjects :
- Animals
Behavior, Animal
Dendritic Spines pathology
Dendritic Spines ultrastructure
Hyperalgesia prevention & control
Macrophage Activation
Male
Mice
Mice, Inbred C57BL
Microglia
Neuralgia psychology
Spinal Cord metabolism
Spinal Cord pathology
Bone Marrow Transplantation methods
Diterpenes toxicity
MAP Kinase Signaling System drug effects
Mesenchymal Stem Cell Transplantation methods
Neuralgia chemically induced
Neuralgia prevention & control
Protein Kinase C-delta antagonists & inhibitors
TRPA1 Cation Channel antagonists & inhibitors
Transcription Factor RelA drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2747
- Volume :
- 174
- Database :
- MEDLINE
- Journal :
- Brain research bulletin
- Publication Type :
- Academic Journal
- Accession number :
- 34098041
- Full Text :
- https://doi.org/10.1016/j.brainresbull.2021.06.004