RIP3 Inhibition ameliorates chronic constriction injury-induced neuropathic pain by suppressing JNK signaling

AGING, 2021 · DOI: · Published: November 12, 2021

Simple Explanation

Neuropathic pain (NP) is a chronic condition where even harmless stimuli cause pain. Current treatments have limited efficacy and severe side effects, highlighting the need for better solutions. This study explores the role of Receptor Interacting Serine/Threonine Kinase 3 (RIP3) and its influence on JNK signaling in neuropathic pain induced by chronic constriction injury (CCI). The research also investigates the effects of sinomenine, a natural compound known for its anti-inflammatory properties, on RIP3 and neuropathic pain.

Study Duration

Not specified

Participants

Adult male Sprague-Dawley rats (200−250 g)

Evidence Level

Not specified

Key Findings

1
RIP3 inhibitors (GSK’872) and JNK inhibitors (SP600125) alleviated pain and reduced inflammatory factor levels in CCI rats.
2
Sinomenine treatment reduced RIP3, p-JNK and c-Fos levels in the spinal cords of CCI rats, suggesting it alleviates neuropathic pain by suppressing JNK signaling.
3
Inhibiting RIP3 significantly suppressed JNK in the spinal cord, and RIP3 induces neuronal damage by stimulating JNK signaling.

Research Summary

This study investigates the role of RIP3-induced JNK signaling in chronic constriction injury (CCI)-induced neuropathic pain. The findings demonstrate that RIP3 inhibition alleviates neuropathic pain by suppressing JNK signaling, particularly via sinomenine treatment. The research suggests that RIP3 could be a new treatment target in patients with neuropathic pain.

Practical Implications

New Therapeutic Target

RIP3 could be considered as a new treatment target for neuropathic pain.

Potential of Sinomenine

Sinomenine has great clinical potential for the treatment of neuropathic pain.

Underlying Mechanisms

Antagonizing RIP3 could prevent the activation of the JNK pathway and exert anti-nociceptive effects in a model of NP.

Study Limitations

1
The mechanism and applicability of sinomenine need to be further verified.
2
The study focuses on CCI-induced neuropathic pain in rats, and further research is needed to confirm these findings in humans.
3
The specific target of sinomenine has not yet been discovered.

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