CC BY-NC 4.0 · Arch Plast Surg 2015; 42(06): 695-703
DOI: 10.5999/aps.2015.42.6.695
Original Article

The Vasodilator Effect of a Cream Containing 10% Menthol and 15% Methyl Salicylate on Random-Pattern Skin Flaps in Rats

Utku Can Dölen
Department of Plastic Surgery, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey
Nezih Sungur
Plastic Surgery Clinic, Ankara Training and Research Hospital, Ankara, Turkey
Gökhan Koca
Department of Nuclear Medicine, Ankara Training and Research Hospital, Ankara, Turkey
Onur Ertunç
Department of Pathology, Medical School of Gazi University, Ankara, Turkey
Ayşe Tülay Bağcı Bosi
Department of Public Health, Medical School of Hacettepe University, Ankara, Turkey
Uğur Koçer
Plastic Surgery Clinic, Ankara Training and Research Hospital, Ankara, Turkey
Meliha Korkmaz
Department of Nuclear Medicine, Ankara Training and Research Hospital, Ankara, Turkey
› Author Affiliations

Background It is still difficult to prevent partial or full-thickness flap necrosis. In this study, the effects of a cream containing menthol and methyl salicylate on the viability of randompattern skin flaps were studied.

Methods Forty female Sprague-Dawley rats were divided into two equal groups. Caudally based dorsal random-pattern skin flaps were elevated, including the panniculus carnosus. In the study group, 1.5 mL of a cream containing menthol and methyl salicylate was applied to the skin of the flap, and saline solution (0.9%) was used in the control group. Upon completion of the experiment, flap necrosis was analyzed with imaging software and radionuclide scintigraphy. Histopathological measurements were made of the percentage of viable flaps, the number of vessels, and the width of the panniculus carnosus muscle.

Results According to the photographic analysis, the mean viable flap surface area in the study group was larger than that in the control group (P=0.004). According to the scintigrams, no change in radioactivity uptake was seen in the study group (P>0.05). However, a significant decrease was observed in the control group (P=0.006). No statistically significant differences were observed between the groups in terms of the percentage of viable flaps, the number of vessels, or the width of the panniculus carnosus muscle (P>0.05).

Conclusions Based on these results, it is certain that the cream did not reduce the viability of the flaps. Due to its vasodilatory effect, it can be used as a component of the dressing in reconstructive operations where skin perfusion is compromised.

Publication History

Received: 10 February 2015

Accepted: 17 August 2015

Article published online:
05 May 2022

© 2015. The Korean Society of Plastic and Reconstructive Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonCommercial License, permitting unrestricted noncommercial use, distribution, and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes. (

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

  • References

  • 1 Rinker B, Fink BF, Barry NG. et al. The effect of calcium channel blockers on smoking-induced skin flap necrosis. Plast Reconstr Surg 2010; 125: 866-871
  • 2 Chen W, Yang D, Wang P. et al. Microencapsulated myoblasts transduced by the vascular endothelial growth factor (VEGF) gene for the ischemic skin flap. Aesthetic Plast Surg 2011; 35: 326-332
  • 3 Miyawaki T, Jackson IT, Bier UC. et al. The effect of capsaicin ointment on skin for the survival of a cutaneous flap. Eur J Plast Surg 2001; 24: 28-30
  • 4 Pal S, Khazanchi RK, Moudgil K. An experimental study on the effect of nifedipine on ischaemic skin flap survival in rats. Br J Plast Surg 1991; 44: 299-301
  • 5 Stadelmann WK, Hess DB, Robson MC. et al. Aprotinin in ischemia-reperfusion injury: flap survival and neutrophil response in a rat skin flap model. Microsurgery 1998; 18: 354-361
  • 6 Patel T, Ishiuji Y, Yosipovitch G. Menthol: a refreshing look at this ancient compound. J Am Acad Dermatol 2007; 57: 873-878
  • 7 Kamatou GP, Vermaak I, Viljoen AM. et al. Menthol: a simple monoterpene with remarkable biological properties. Phytochemistry 2013; 96: 15-25
  • 8 Johnson CD, Melanaphy D, Purse A. et al. Transient receptor potential melastatin 8 channel involvement in the regulation of vascular tone. Am J Physiol Heart Circ Physiol 2009; 296: H1868-H1877
  • 9 Namer B, Seifert F, Handwerker HO. et al. TRPA1 and TRPM8 activation in humans: effects of cinnamaldehyde and menthol. Neuroreport 2005; 16: 955-959
  • 10 Olive JL, Hollis B, Mattson E. et al. Vascular conductance is reduced after menthol or cold application. Clin J Sport Med 2010; 20: 372-376
  • 11 Topp R, Winchester LJ, Schilero J. et al. Effect of topical menthol on ipsilateral and contralateral superficial blood flow following a bout of maximum voluntary muscle contraction. Int J Sports Phys Ther 2011; 6: 83-91
  • 12 Chotani MA, Flavahan S, Mitra S. et al. Silent alpha(2C)-adrenergic receptors enable cold-induced vasoconstriction in cutaneous arteries. Am J Physiol Heart Circ Physiol 2000; 278: H1075-H1083
  • 13 Green DJ, O'Driscoll G, Blanksby BA. et al. Control of skeletal muscle blood flow during dynamic exercise: contribution of endothelium-derived nitric oxide. Sports Med 1996; 21: 119-146
  • 14 Ohta T, Imagawa T, Ito S. Involvement of transient receptor potential vanilloid subtype 1 in analgesic action of methylsalicylate. Mol Pharmacol 2009; 75: 307-317
  • 15 Davis RE, Wachholz JH, Jassir D. et al. Comparison of topical anti-ischemic agents in the salvage of failing random-pattern skin flaps in rats. Arch Facial Plast Surg 1999; 1: 27-32
  • 16 Hong CZ, Shellock FG. Effects of a topically applied counterirritant (Eucalyptamint) on cutaneous blood flow and on skin and muscle temperatures: a placebo-controlled study. Am J Phys Med Rehabil 1991; 70: 29-33
  • 17 Kunta JR, Goskonda VR, Brotherton HO. et al. Effect of menthol and related terpenes on the percutaneous absorption of propranolol across excised hairless mouse skin. J Pharm Sci 1997; 86: 1369-1373
  • 18 Martin D, Valdez J, Boren J. et al. Dermal absorption of camphor, menthol, and methyl salicylate in humans. J Clin Pharmacol 2004; 44: 1151-1157
  • 19 Hammond DC, Brooksher RD, Mann RJ. et al. The dorsal skin-flap model in the rat: factors influencing survival. Plast Reconstr Surg 1993; 91: 316-321
  • 20 Jones M, Zhang F, Blain B. et al. Influence of recipient-bed isolation on survival rates of skin-flap transfer in rats. J Reconstr Microsurg 2001; 17: 653-658
  • 21 Cheon YW, Tark KC, Kim YW. Better survival of random pattern skin flaps through the use of epigallocatechin gallate. Dermatol Surg 2012; 38: 1835-1842
  • 22 Komorowska-Timek E, Chen SG, Zhang F. et al. Prolonged perivascular use of verapamil or lidocaine decreases skin flap necrosis. Ann Plast Surg 1999; 43: 283-288
  • 23 Cheang WS, Lam MY, Wong WT. et al. Menthol relaxes rat aortae, mesenteric and coronary arteries by inhibiting calcium influx. Eur J Pharmacol 2013; 702: 79-84
  • 24 Topp R, Ledford ER, Jacks DE. Topical menthol, ice, peripheral blood flow, and perceived discomfort. J Athl Train 2013; 48: 220-225
  • 25 Ghavami A, Nutt MP, Hardy SP. Heat shock protein and high-dose aspirin: effects on random skin flap survival in a rat model. Ann Plast Surg 2002; 48: 60-67