Correlation of TGN-020 with the analgesic effects via ERK pathway activation after chronic constriction injury.

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-1β, 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.

• Authors: Liang Zhao, Dan Li, Nan Liu, Lu Liu, Zhuo Zhang, Chao Gao, Hitoshi Kawano, Fang-Yuan Zhou, Hong-Peng Li
• Journal: Molecular pain (Mol Pain) 2018 Jan-Dec Vol. 14 Pg. 1744806918796057 ISSN: 1744-8069 [Electronic] United States
• PMID: 30152258 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(nicotinamide)-1,3,4-thiadiazole
• Analgesics
• Aquaporin 4
• Thiadiazoles
• Niacinamide
• Mitogen-Activated Protein Kinase Kinases
• Phosphopyruvate Hydratase

Topics

• Analgesics (therapeutic use)
• Animals
• Aquaporin 4 (antagonists & inhibitors, metabolism)
• Disease Models, Animal
• Hyperalgesia (drug therapy, etiology)
• MAP Kinase Signaling System (drug effects)
• Male
• Mitogen-Activated Protein Kinase Kinases (metabolism)
• Neuralgia (drug therapy)
• Niacinamide (analogs & derivatives, therapeutic use)
• Pain Threshold (drug effects)
• Phosphopyruvate Hydratase (metabolism)
• Rats
• Rats, Sprague-Dawley
• Thiadiazoles (therapeutic use)
• Up-Regulation (drug effects)