The present study demonstrates that the anti-arthritic effect of SIN is dependent on the integrity of vagus nerve, and its anti-inflammatory mechanism can be summarized step-by-step as: stimulation of α7nAChR – activation of PI3K/Akt/mTOR pathway – generation of anti-inflammatory neuropeptide VIP from the nicotinic cholinergic nerves in small intestine – VIP enters systemic circulation to attenuate inflammatory response. Here, VIP is linked to squamous cell intraepithelial neoplasia.