Impact of Morphine Dependency on Secondary Intention Wound Healing in Rat

  • Jalal Vahedian-Ardakani Department of Surgery, Firoozgar Hospital, Tehran University of Medical Sciences, Tehran, Iran.
  • Massoud Baghai-Wadji Department of Surgery, Firoozgar Hospital, Tehran University of Medical Sciences, Tehran, Iran.
  • Shahram Nazerani Department of Surgery, Firoozgar Hospital, Tehran University of Medical Sciences, Tehran, Iran.
  • Mohammad Reza Keramati Department of Surgery, Firoozgar Hospital, Tehran University of Medical Sciences, Tehran, Iran.
  • Tooraj-Reza Mirshekari Department of Pathology, Shafa Hospital, Kerman University of Medical Sciences, Kerman, Iran.
  • Kayvan Ansari Department of Surgery, Firoozgar Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Keywords:
Wound healing, Morphine, Addiction, Rat

Abstract

Wound healing has always been among important and crucial subjects in medicine. Morphine dependency has also been a social and health problem in the Middle East. This study was aimed to investigate the effects of morphine dependency on pro-inflammatory and fibroblast cell recruitment, as well as re-epithelialization and the revascularization processes involved in secondary intention wound healing in rats. A full-thickness wound (2×2 cm in diameters) was created on the dorsum of two groups of rats, a control group and a second group consisted of morphine dependent rats. During the first 14 days of post wounding the wound was excised consecutively at priorly planned days with peripheral margins of normal skin. The specimens were evaluated by two pathologists, who were blind to the study design, and the cellular population, re-epithelialization and revascularization were reported by them. Histological examination of the wound tissue showed evidence of increased population of fibroblasts and a plateau or decreased recruitment of macrophage and neutrophile cells. In the dependent group re-epithelialization was observed to be enhanced significantly in comparison to the control group while having an inhibitory effect on revascularization. The present study demonstrates that morphine dependency enhances re-epithelialization as well as tissue recruitment of fibroblasts; thereby probably enhancing secondary intention wound healing.

References

Martin JL, Charboneau R, Barke RA, Roy S. Chronic morphine treatment inhibits LPS-induced angiogenesis: implications in wound healing. Cell Immunol 2010;265(2):139-45.

Martin JL, Koodie L, Krishnan AG, Charboneau R, Barke RA, Roy S. Chronic morphine administration delays wound healing by inhibiting immune cell recruitment to the wound site. Am J Pathol 2010;176(2):786-99.

Lam CF, Chang PJ, Huang YS, Sung YH, Huang CC, Lin MW, Liu YC, Tsai YC. Prolonged use of high-dose morphine impairs angiogenesis and mobilization of endothelial progenitor cells in mice. Anesth Analg 2008;107(2):686-92.

Singhal PC, Sharma P, Sanwal V, Prasad A, Kapasi A, Ranjan R, Franki N, Reddy K, Gibbons N. Morphine modulates proliferation of kidney fibroblasts. Kidney Int 1998;53(2):350-7.

Singhal PC, Sharma P, Gibbons N, Franki N, Kapasi A, Wagner JD. Effect of morphine on renomedullary interstitial cell proliferation and matrix accumulation. Nephron 1997;77(2):225-34.

Singhal PC, Gibbons N, Abramovici M. Long term effects of morphine on mesangial cell proliferation and matrix synthesis. Kidney Int 1992;41(6):1560-70.

Badawy AA, Evans CM, Evans M. Production of tolerance and physical dependence in the rat by simple administration of morphine in drinking water. Br J Pharmacol 1982;75(3):485-91.

Stadelmann WK, Digenis AG, Tobin GR. Impediments to wound healing. Am J Surg 1998;176(2A Suppl):39S-47S.

Singer AJ, Quinn JV, Thode HC Jr, Hollander JE; TraumaSeal Study Group. Determinants of poor outcome after laceration and surgical incision repair. Plast Reconstr Surg 2002;110(2):429-35; discussion 436-7.

Barbul A, Efron DT. Wound healing. In: Brunicardi FC, Andersen DK, Billiar TR, Dunn DL, Hunter JG, Matthews JB, Pollock RE. Schwart’s Principles of Surgery. 9th ed. New York: McGraw Hill; 2010.

Midwood KS, Williams LV, Schwarzbauer JE. Tissue repair and the dynamics of the extracellular matrix. Int J Biochem Cell Biol 2004;36(6):1031-7.

Chang HY, Sneddon JB, Alizadeh AA, Sood R, West RB, Montgomery K, Chi JT, van de Rijn M, Botstein D, Brown PO. Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds. PLoS Biol 2004;2(2):E7.

Garg HG. Scarless Wound Healing. New York: Marcel Dekker Inc; 2000.

Enoch S, Price P. Cellular, molecular and biochemical differences in the pathophysiology of healing between acute wounds, chronic wounds and wounds in the elderly. [Internet] 2004 Aug [cited 2012 May]; Available from: http://www.worldwidewounds.com/2004/august/Enoch/Pat hophysiology-Of-Healing.html

Singhal PC, Sharma P, Sanwal V, Prasad A, Kapasi A, Ranjan R, Franki N, Reddy K, Gibbons N. Morphine modulates proliferation of kidney fibroblasts. Kidney Int 1998;53(2):350-7.

Singhal PC, Sharma P, Gibbons N, Franki N, Kapasi A, Wagner JD. Effect of morphine on renomedullary interstitial cell proliferation and matrix accumulation. Nephron 1997;77(2):225-34.

Singhal PC, Gibbons N, Abramovici M. Long term effects of morphine on mesangial cell proliferation and matrix synthesis. Kidney Int 1992;41(6):1560-70.

Chang PJ, Chen MY, Huang YS, Lee CH, Huang CC, Lam CF, Tsai YC. Morphine enhances tissue content of collagen and increases wound tensile strength. J Anesth 2010;24(2):240-6.

Wikimedia Foundation Inc. Wound healing. Wikipedia the free encyclopedia. [Internet] Available from: http://en.wikipedia.org/wiki/Wound_healing

How to Cite
1.
Vahedian-Ardakani J, Baghai-Wadji M, Nazerani S, Keramati MR, Mirshekari T-R, Ansari K. Impact of Morphine Dependency on Secondary Intention Wound Healing in Rat. Acta Med Iran. 50(6):380-387.
Section
Articles