Chronic pain is highly prevalent. Individuals with cognitive disorders such as Alzheimer’s disease are susceptible population in which pain is frequently difficult to diagnosis. It is still unclear whether the pathological changes in Alzheimer’s disease patients will affect the pain processing. Here we leverage animal behavior, neural activity recording, optogenetics, chemogenetics and Alzheimer’s disease modeling to examine the contribution of the anterior cingulate cortex (ACC) neurons to the pain response. The 5× familial Alzheimer’s disease (5×FAD) mice show alleviated mechanical allodynia which can be regained by genetic activation of ACC excitatory neurons. Furthermore, the lower peak neuronal excitation, delayed response initiation as well as the dendritic spine reduction of ACC pyramidal neurons in 5×FAD mice can be mimicked by Rac1 or actin polymerization inhibitor in Wild-type (WT) mice. These findings indicate that abnormal of pain sensitivity in Alzheimer’s disease modeling mice is closely related to the variation of neuronal activity and dendritic spine loss in ACC pyramidal neurons, suggesting the crucial role of dendritic spine density in pain processing.
Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.