The PKC neurons in anterior cingulate cortex contribute to the development of neuropathic allodynia and pain-related emotion

Background: While the PKC gamma neurons in spinal dorsal horn play an indispensable part in neuropathic allodynia, the exact effect of PKC gamma neurons of brain regions in neuropathic pain remains elusive. Mounting research studies have depicted that the anterior cingulate cortex (ACC) is closely linked with pain perception and behavior, the present study was designed to investigate the contribution of PKC gamma neurons in ACC to neuropathic allodynia and pain-related emotion in newly developed Prkcg-P2A-Tdtomato mice. Methods: The c-fos expression in response to innocuous stimulation was used to monitor the activity of PKC gamma in CCI (chronic constriction injury of the sciatic nerve) induced neuropathic pain condition. Activating or silencing ACC PKC gamma neurons by chemogenetics was applied to observe the changes of pain behavior. The excitability of ACC PKC gamma neurons in normal and CCI mice was compared by patch-clamp whole-cell recordings. Results: The PKC gamma-Tdtomato neurons were mainly distributed in layer III-Vof ACC. The Tdtomato was mainly expressed in ACC pyramidal neurons demonstrated by intracellular staining. The c-fos expression in ACC PKC gamma neurons in response to innocuous stimulation was obviously elevated in CCI mice. The patch clamp recordings showed that ACC PKC gamma-Tdtomato neurons were largely activated in CCI mice. Chemogenetic activation of ACC PKC gamma neurons in Prkcg-icre mice induced mechanical allodynia and pain-related aversive behavior, conversely, silencing them in CCI condition significantly reversed the mechanical allodynia and pain-related place aversive behavior. Conclusion: We conclude that the PKC gamma neurons in ACC are closely linked with neuropathic allodynia and pain-related emotional behaviors.