Critical Role of p38α MAPK Subclass in the Development of Pain Hypersensitivity After Hind Paw Incision.

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.