Morphine enhances tissue content of collagen and increases wound tensile strength

Abstract

Morphine is a commonly prescribed analgesic for wound pain. Previous studies have shown that morphine enhances accumulation of collagen in cultured fibroblasts. Because fibroblasts are important for the remodeling of connective tissue in incisional wound, this study investigates the biological effects of morphine on cutaneous collagen content and wound tensile strength. A full-thickness incisional wound (2 cm in length) was created on the dorsum of mice followed by treatment with placebo or morphine (5 and 20 mg/kg/day, i.p.). Fourteen days later, tensile strength of the healed incisional wound was measured using a tensiometer. Protein expression of transforming growth factor (TGF)-beta1 and matrix metalloproteinases (MMP)-2 in the incisional wound tissue was analyzed. Degree of tissue remodeling and levels of collagen were determined by histological examination and a dye-binding collagen assay, respectively. Morphine enhanced the breaking strength of incisional wound 14 days after treatment (92 +/- 10, 102 +/- 10 and 134 +/- 12 mg for control, morphine 5 mg/kg/day and morphine 20 mg/kg/day, respectively; P = 0.03, n = 6-7). Protein expression of TGF-beta1 and MMP-2 was significantly enhanced in mice treated with morphine. Histological examination of the wound tissue showed evidence of increased thickness of the cutaneous fibrous layer and deposition of collagen in the high-dose morphine treatment group. Collagen assays also demonstrated that tissue concentrations of collagen were significantly increased in the wound tissue of morphine-treated animals on day 2 of drug treatment. The present study demonstrates that systemic administration of morphine enhances tissue collagen deposition in the cutaneous tissue, thereby increasing the tensile strength of the incisional wound.