The mechanisms of fibroproliferation disease (FPD) of the skin, such as keloids and hypertrophic scars, are still unknown. Since mechanical stress appears to be an important factor for FPD generation, we have studied the intervening factors that connect mechanical stress with keloid and scar formation. Hence, we introduce our "neurogenic inflammation hypothesis" in this paper. Our hypothesis is as follows. Mechanical stress, including skin stretching, stimulates mechanosensitive nociceptors on sensory fibers in the skin. Stimulated fibers release neuropeptides, including SP and CGRP, and these peptides bind to the receptors SP-NK1R and CGRP-CGRP1R on various cells in the skin. Moreover, histamine release is upregulated by mast cells. Consequently, activated endothelial cells and vascular smooth muscle cells induce vasodilation and permeabilization of vessels. Cytokine production, including TGFbeta and NGF, is also stimulated by various cells. The neurogenic inflammation and upregulation of TGFbeta would activate fibroblasts through various signals. Interestingly, overexpressed NGF may induce the hyper-release of neuropeptides from sensory fibers, resulting in the accumulation of neuropeptides even in the absence of mechanical stress, once the malignant cycle has started. Moreover, individual differences in FPD generation may be based on differences in reactivity towards neuropeptides, NGF, and other neurotrophins. Hence, neuropeptide antagonists may be effective against FPD. While further experimental studies and clinical confirmation are needed, our hypothesis may provide new insights into the etiology and pathology of FPD of the skin, such as keloids and hypertrophic scars.