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 behaviors. 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 behaviors 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 naïve 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 behavioral impairments. Together, our findings provide novel insights into the role of PL excitatory neurons in the regulation of sensory and affective pain.

Guo-Qiang Wang, Cheng Cen, Chong Li, Shuai Cao, Ning Wang, Zheng Zhou, Xue-Mei Liu, Yu Xu, Na-Xi Tian, Ying Zhang, Jun Wang, Li-Ping Wang & Yun Wang(2015). Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety.  Nature Communications.  doi:10.1038/ncomms8660.