Aim: The medial prefrontal context (mPFC) plays pivotal roles in initiation, development, and maintenance of chronic pain, whereas the underlying molecular mechanisms remain elusive, which invited investigation of potential involvement of MKP1 in mPFC in mice in neuropathic pain, and its cellular and molecular mechanisms.

Materials and methods: Neuropathic pain model was established in adult male Kunming mice via chronic constrictive injury (CCI) of the sciatic nerve. Paw withdrawal latency (PWL) was measured at the plantar area by radiant heat test. Stereotaxic microinjection was applied in mice as per the atlas of Mouse Brain in Stereotaxic Coordinates. mRNA levels of MKP1 in mPFC in CCI mice were assessed by RT-PCR; protein expressions of MKP1, p-p38, p-JNK and p-ERK in mPFC in CCI mice were analyzed by Western blotting, and expressions of the c-Fos in mPFC in CCI mice evaluated by immunohistochemistry. Moreover, Lenti-MKP1 particles or BCI treatment was employed to inhibit MKP1 in mPFC contralateral to the injury.

Results: MKP1 was activated and persistently upregulated in mPFC neurons in CCI mice. Inhibition of MKP1 in the mPFC contralateral to the injury could reverse CCI-induced pain behavior and neuronal activity either via employment of Lenti-MKP1 particles or BCI treatment. MKP1 in the mPFC modulated neuropathic pain via dephosphorization of p38 and JNK1/2.

Conclusion: The findings demonstrated that MKP1 in mPFC could play a paramount role in the modulation of neuropathic pain, which might be associated to the increased neuronal excitability in the mPFC and downregulated p-p38 and p-JNK expression.

目的：内侧前额叶背景（mPFC）在慢性疼痛的发生，发展和维持中起关键作用，而潜在的分子机制仍然难以捉摸，这促使人们对神经性疼痛小鼠及其细胞中MKP1可能参与mPFC的研究进行了研究。和分子机制。

材料和方法：通过坐骨神经慢性收缩损伤（CCI）在成年雄性昆明小鼠中建立神经性疼痛模型。通过辐射热测试在足底区域测量爪缩回潜伏期（PWL）。根据立体定向坐标系中的小鼠脑图集对小鼠进行立体定向显微注射。RT-PCR法检测CCI小鼠mPFC中MKP1的mRNA水平。通过蛋白质印迹法分析CCI小鼠mPFC中MKP1，p-p38，p-JNK和p-ERK的蛋白表达，并通过免疫组化评估c-Fos在CCI小鼠mPFC中的表达。此外，采用Lenti-MKP1颗粒或BCI处理来抑制与损伤相反的mPFC中的MKP1。

结果： MKP1在CCI小鼠的mPFC神经元中被激活并持续上调。通过使用Lenti-MKP1颗粒或BCI治疗，在与损伤相反的mPFC中抑制MKP1可以逆转CCI诱导的疼痛行为和神经元活动。mPFC中的MKP1通过p38和JNK1 / 2的脱磷调节神经性疼痛。

结论：研究结果表明，mPFC中的MKP1在调节神经性疼痛中起着至关重要的作用，这可能与mPFC中神经元兴奋性增加以及p-p38和p-JNK表达下调有关。