MKP1 in the medial prefrontal cortex modulates chronic neuropathic pain via regulation of p38 and JNK1/2.

Yiling Qian, Zhiyong Wang, Siqi Zhou, Weinan Zhao, Cui Yin, Junli Cao, Zhiping Wang, Yanqiang Li

The International journal of neuroscience 2020 Jul

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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.

Citation

Yiling Qian, Zhiyong Wang, Siqi Zhou, Weinan Zhao, Cui Yin, Junli Cao, Zhiping Wang, Yanqiang Li. MKP1 in the medial prefrontal cortex modulates chronic neuropathic pain via regulation of p38 and JNK1/2. The International journal of neuroscience. 2020 Jul;130(7):643-652