Delayed inhibition of ERK and p38 attenuates neuropathic pain without affecting motor function recovery after peripheral nerve injury.

Abstract

Peripheral nerve injuries (PNIs) often result in persistent neuropathic pain, seriously affecting quality of life. Existing therapeutic interventions for PNI-induced neuropathic pain are far from satisfactory. Extracellular signal-regulated kinases (ERKs) and p38 have been found to participate in triggering and maintaining PNI-induced neuropathic pain. However, ERK and p38 also contribute to axonal regeneration and motor function recovery after PNI, making it difficult to inhibit ERK and p38 for therapeutic purposes. In this study, we simultaneously characterized neuropathic pain and motor function recovery in a mouse sciatic nerve crush injury model to identify the time window for therapeutic interventions. We further demonstrated that delayed delivery of a combination of ERK and p38 inhibitors at three weeks after PNI could significantly alleviate PNI-induced neuropathic pain without affecting motor function recovery. Additionally, the combined use of these two inhibitors could suppress pain markedly better than either inhibitor alone, possibly reducing the required dose of each inhibitor and alleviating the side effects and risks of the inhibitors when used individually.

• Authors: SaiSai Huang, YingTing Chen, Yue Jia, Tuo Yang, WenFeng Su, ZhenYu Zhu, Peng Xue, FeiFan Feng, YaYu Zhao, Gang Chen
• Journal: Neuropharmacology (Neuropharmacology) Vol. 202 Pg. 108835 (01 01 2022) ISSN: 1873-7064 [Electronic] England
• PMID: 34648772 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Butadienes
• Enzyme Inhibitors
• Imidazoles
• Nitriles
• Pyridines
• U 0126
• Extracellular Signal-Regulated MAP Kinases
• p38 Mitogen-Activated Protein Kinases
• SB 203580

Topics

• Animals
• Axons (physiology)
• Butadienes (pharmacology, therapeutic use)
• Disease Models, Animal
• Enzyme Inhibitors (pharmacology, therapeutic use)
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors, metabolism, physiology)
• Imidazoles (pharmacology, therapeutic use)
• Male
• Mice, Inbred C57BL
• Nerve Regeneration (genetics)
• Neuralgia (drug therapy, etiology, genetics)
• Nitriles (pharmacology, therapeutic use)
• Peripheral Nerve Injuries (complications, physiopathology)
• Pyridines (pharmacology, therapeutic use)
• Recovery of Function
• Sciatic Nerve (injuries, physiopathology)
• Treatment Outcome
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors, metabolism, physiology)
• Mice