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Analysis of Neuropeptides in Stretched Skin

Chin, Michael S. B.A.; Lancerotto, Luca M.D.; Helm, Douglas L. M.D.; Dastouri, Pouya M.D.; Prsa, Michael J. B.S.; Ottensmeyer, Mark Ph.D.; Akaishi, Satoshi M.D., Ph.D.; Orgill, Dennis P. M.D., Ph.D.; Ogawa, Rei M.D., Ph.D.

Plastic and Reconstructive Surgery: July 2009 - Volume 124 - Issue 1 - p 102-113
doi: 10.1097/PRS.0b013e3181a81542
EXPERIMENTAL: ORIGINAL ARTICLES
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Background: Mechanical forces modulate wound healing and scar formation through mechanotransduction. In response to mechanical stimulation, neuropeptides are released from peripheral terminals of primary afferent sensory neurons, influencing skin and immune cell functions and increasing vascular permeability, causing neurogenic inflammation.

Methods: A computer-controlled device was used to stretch murine skin. C57Bl6 mice (n = 26) were assigned to a cyclical square-wave tensile stimulation for 4 hours or continuous stimulation for 4 hours. Stretched skin was analyzed for expression of the neuropeptides, substance P and calcitonin gene-related peptide, their receptors (NK1R and calcitonin gene-related peptide receptor component protein), and growth factors (nerve growth factor, transforming growth factor β1, vascular endothelial growth factor, and epidermal growth factor) using immunohistochemistry and real-time reverse-transcriptase polymerase chain reaction.

Results: Cyclical stimulation resulted in a significant increase in expression of neuropeptides and growth factors, whereas the corresponding peptide receptors were down-regulated. Transcription of neuropeptide mRNA was elevated in stretched skin, which proves that neuropeptides are released from not only peripheral terminals of nerve fibers but also resident skin cells.

Conclusions: The authors' results suggest that skin stretching may alter cell physiology by stimulating neuropeptide expression, and that cyclical mechanical force may be more effectively stimulating mechanosensitive nociceptors or mechanoreceptors (mechanosensors) on cells.

Boston and Cambridge, Mass.; Padua, Italy; and Tokyo, Japan

From the Tissue Engineering and Wound Healing Laboratory, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School; Tufts University School of Medicine; the University of Padua; the Department of Electronics and Mechanical, Wentworth Institute of Technology; simulation group, CIMIT, Massachusetts Institute of Technology; and the Department of Plastic, Reconstructive, and Aesthetic Surgery, Nippon Medical School.

Received for publication November 14, 2008; accepted January 7, 2009.

Rei Ogawa, M.D., Ph.D., Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. 02115, r.ogawa@nms.ac.jp

Disclosure:This study was supported by the authors' own funds; none of the authors has a financial interest in any of the products, devices, or drugs mentioned in the article.

©2009American Society of Plastic Surgeons