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RIP3 Inhibition ameliorates chronic constriction injury-induced neuropathic pain by suppressing JNK signaling
- Source :
- Aging (Albany NY)
- Publication Year :
- 2021
- Publisher :
- Impact Journals, 2021.
-
Abstract
- Neuroinflammation is a major contributor to neuropathic pain. Receptor interacting serine/threonine kinase 3 (RIP3) senses cellular stress, promotes inflammatory responses and activates c-Jun N-terminal kinase (JNK) signaling. Here, we assessed the involvement of RIP3-induced JNK signaling in chronic constriction injury (CCI)-induced neuropathic pain. We found that RIP3 inhibitors (GSK’872) and JNK inhibitors (SP600125) not only alleviated the radiant heat response and mechanical allodynia in CCI rats, but also reduced inflammatory factor levels in the lumbar spinal cord. CCI surgery induced RIP3 mRNA and protein expression in the spinal cord. GSK’872 treatment after CCI surgery reduced RIP3 and phosphorylated (p)-JNK expression in the spinal cord, whereas SP600125 treatment after CCI surgery had almost no effect on RIP3. Sinomenine treatment reduced RIP3, p-JNK and c-Fos levels in the spinal cords of CCI rats. These data demonstrated that RIP3 inhibition (particularly via sinomenine treatment) alleviates neuropathic pain by suppressing JNK signaling. RIP3 could thus be a new treatment target in patients with neuropathic pain.
- Subjects :
- Male
Aging
sinomenine
serine-threonine kinases receptor-interacting protein 3 (RIP3)
Pharmacology
neuroinflammation
Cell Line
Rats, Sprague-Dawley
medicine
Animals
Benzothiazoles
Receptor
Sinomenine
Neuroinflammation
neuropathic pain
Anthracenes
Kinase
business.industry
c-Jun N-terminal kinase (JNK)
JNK Mitogen-Activated Protein Kinases
Cell Biology
Spinal cord
Constriction
nervous system diseases
Rats
Lumbar Spinal Cord
medicine.anatomical_structure
Receptor-Interacting Protein Serine-Threonine Kinases
Neuropathic pain
Neuroinflammatory Diseases
Quinolines
Phosphorylation
Neuralgia
business
psychological phenomena and processes
Research Paper
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 19454589
- Volume :
- 13
- Issue :
- 21
- Database :
- OpenAIRE
- Journal :
- Aging (Albany NY)
- Accession number :
- edsair.doi.dedup.....5e1256e16165c3cfca9db79253857345