Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety

The medial prefrontal cortex (mPFC) is implicated in processing sensory-discriminative and affective pain. Nonetheless, the underlying mechanisms are poorly understood. Here we demonstrate a role for excitatory neurons in the prelimbic cortex (PL), a sub-region of mPFC, in the regulation of pain sensation and anxiety-like behaviours. Using a chronic inflammatory pain model, we show that lesion of the PL contralateral but not ipsilateral to the inflamed paw attenuates hyperalgesia and anxiety-like behaviours in rats. Optogenetic activation of contralateral PL excitatory neurons exerts analgesic and anxiolytic effects in mice subjected to chronic pain, whereas inhibition is anxiogenic in naive mice. The intrinsic excitability of contralateral PL excitatory neurons is decreased in chronic pain rats; knocking down cyclin-dependent kinase 5 reverses this deactivation and alleviates behavioural impairments. Together, our findings provide novel insights into the role of PL excitatory neurons in the regulation of sensory and affective pain.Ministry of Science and Technology of China (973 Program) [2014CB542204]; National Natural Science Foundation of China [91332119, 81161120497, 30925015, 31371143, 91132306, 31471119]; National Science Foundation for distinguished young scholars of China [81425010]; Strategic Priority Research Program [XDB02050003]; Beijing Higher Education Young Elite Teacher Project [YEPT0051]; Beijing Natural Science Foundation [7132130]; open project of the Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of SciencesSCI(E)PubMedARTICLElp.wang@siat.ac.cn; wangy66@bjmu.edu.cn7660