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Updated: May 25, 2025

Chronic Post-Ischemia Pain Model for Complex Regional Pain Syndrome Type-I in Rats
Published on: January 21, 2020
Critical Role of p38α MAPK Subclass in the Development of Pain Hypersensitivity After Hind Paw Incision
Daiki Ishikawa1, Shunsuke Yamakita1, Kentaro Oh-Hashi2,3,4
1Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Background:
Deeper understanding of the mechanisms of postoperative pain is critical for developing more effective pain management strategies. The present animal study explored the function of four p38 mitogen-activated protein kinase (MAPK) subclasses (α, β, γ, and δ) in dorsal root ganglion (DRG) in the development of post-incisional pain hypersensitivity.
Methods:
The amount of p38 MAPK subclass mRNA in the DRG of male Sprague-Dawley rats was quantified using real-time PCR. Localization of p38 MAPK expression was analyzed by immunohistochemistry using subclass-selective antibodies. The effects of a p38α MAPK inhibitor on plantar incision-induced pain hypersensitivity was assessed using behavioral tests to measure mechanical and thermal sensitivity. The impact of the inhibitor on phosphorylated p38 MAPK expression was also analyzed by immunohistochemistry.
Results:
Four p38 MAPK subclass mRNA were identified in the DRG, with p38α, β, and γ MAPK showing significant expression. p38α and γ MAPK were identified in the DRG neurons, whereas p38β MAPK was distributed in satellite glial cells. Selective inhibition of p38α MAPK reduced both mechanical and thermal hypersensitivity following plantar incision. Treatment with the p38α MAPK inhibitor decreased the expression of phosphorylated p38 MAPK in the DRG.
Conclusion:
These results demonstrated the distinct roles of p38 MAPK subclasses in the DRG, with p38α MAPK playing a dominant role in the development of pain hypersensitivity after tissue injury. Targeting p38α MAPK might be a promising therapeutic strategy for managing postoperative pain.
Insights
Researchers investigated p38 mitogen-activated protein kinase (MAPK) subclasses in dorsal root ganglion (DRG) for postoperative pain. Targeting p38α MAPK significantly reduced pain hypersensitivity, suggesting a potential therapeutic strategy.
Area of Science:
- Neuroscience
- Pain Research
- Molecular Biology
Background:
- Understanding postoperative pain mechanisms is crucial for effective pain management.
- This study investigates the roles of four p38 mitogen-activated protein kinase (MAPK) subclasses in the dorsal root ganglion (DRG) concerning post-incisional pain hypersensitivity.
Purpose of the Study:
- To explore the function of p38 MAPK subclasses (α, β, γ, δ) in the DRG.
- To determine the specific roles of these subclasses in the development of postoperative pain hypersensitivity.
Main Methods:
- Quantified p38 MAPK subclass mRNA in rat DRG using real-time PCR.
- Analyzed p38 MAPK expression localization via immunohistochemistry.
- Assessed the effects of a p38α MAPK inhibitor on pain hypersensitivity using behavioral tests and analyzed its impact on phosphorylated p38 MAPK expression.
Main Results:
- Identified four p38 MAPK subclass mRNAs in DRG, with significant expression of p38α, β, and γ.
- p38α and γ MAPK were found in DRG neurons, while p38β MAPK was in satellite glial cells.
- Selective inhibition of p38α MAPK reduced mechanical and thermal hypersensitivity and decreased phosphorylated p38 MAPK expression.
Conclusions:
- p38α MAPK plays a dominant role in DRG in developing pain hypersensitivity after tissue injury.
- Distinct roles of p38 MAPK subclasses were demonstrated in the DRG.
- Targeting p38α MAPK presents a promising therapeutic strategy for managing postoperative pain.
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