Correlation of TGN-020 with the analgesic effects via ERK pathway activation after chronic constriction injury.
Mol Pain
; 14: 1744806918796057, 2018.
Article
in En
| MEDLINE
| ID: mdl-30152258
ABSTRACT
Extracellular regulated protein kinase (ERK) pathway activation in astrocytes and neurons has been reported to be critical for neuropathic pain development after chronic constriction injury. TGN-020 was found to be the most potent aquaporin 4 inhibitor among the agents studied. The present study aimed to assess whether the inhibition of aquaporin 4 had an analgesic effect on neuropathic pain and whether the inhibition of astrocytic activation and ERK pathway was involved in the analgesic effect of TGN-020. We thus found that TGN-020 upregulated the threshold of thermal and mechanical allodynia, downregulated the expression of interleukin-1ß, interleukin-6, and tumor necrosis factor-α, attenuated the astrocytic activation and suppressed the activation of mitogen-activated protein kinase pathways in the spinal dorsal horn and dorsal root ganglion. Additionally, TGN-020 suppressed ERK phosphorylation in astrocytes and neurons after injury. The findings suggested that the analgesic effects of TGN-020 in neuropathic pain were mediated mainly by the downregulation of chronic constriction injury-induced astrocytic activation and inflammation, which is via the inhibition of ERK pathway in the spinal dorsal horn and dorsal root ganglion.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Thiadiazoles
/
Niacinamide
/
MAP Kinase Signaling System
/
Analgesics
/
Neuralgia
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Animals
Language:
En
Year:
2018
Type:
Article