Screening analyses (ELISA, public databases, flow cytometry, immunofluorescence, etc.)identified pivotal roles of acetylcholine (ACh), α7 nicotinic acetylcholine receptor (α7nAChR), and acetylcholinesterase (AChE) in SD‐aggravated periodontitis with a decrease in ACh levels, down‐regulation of α7nAChR on macrophages, and an increase in trigeminal ganglion‐derived AChE. Here, ACHE is linked to periodontitis.