Akaishi S, Ogawa R, Hyakusoku H, et al.
Medical hypotheses. Date of publication 2008 Jan 1;volume 71(1):32-8.
1. Med Hypotheses. 2008;71(1):32-8. doi: 10.1016/j.mehy.2008.01.032. Epub 2008 Apr
11.
Keloid and hypertrophic scar: neurogenic inflammation hypotheses.
Akaishi S(1), Ogawa R, Hyakusoku H.
Author information:
(1)Department of Plastic, Reconstructive and Aesthetic Surgery, Nippon Medical
School Hospital, 1-1-5 Sendagi Bunkyo-ku, Tokyo, Japan. redstoneqq@yahoo.co.jp
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.
DOI: 10.1016/j.mehy.2008.01.032
PMID: 18406540 [Indexed for MEDLINE]
