کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5829597 | 1558998 | 2012 | 7 صفحه PDF | دانلود رایگان |
Matrix metalloproteinase-9 (MMP-9) is involved in tissue remodeling or neural plasticity in various clinical states (e.g. inflammation, neuropathic pain). We focused on the effect of MMP-9 on development of morphine tolerance after repeated morphine treatment. To develop morphine tolerance, mice were given morphine (10 mg/kg; s.c.) once daily for 5 days. The antinociceptive effect of morphine was measured by the tail flick method. Development of morphine tolerance was significantly inhibited by daily treatment of the non-specific MMP inhibitor GM6001 (5 μg/mouse, i.c.v.). A MMP-9 inhibitor (5 μg/mouse, i.c.v.) partially, yet significantly, inhibited the development of morphine tolerance. Intrathecal treatment of a MMP-9 inhibitor did not affect morphine tolerance. In MMP-9(â/â) mice, the development of morphine tolerance was partially, yet significantly, inhibited compared with wild-type mice. MMP-9 protein expression levels in the midbrain gradually increased 12 h to 24 h after morphine treatment on day 1, but were unchanged on days 3-5. In the spinal cord, MMP-9 protein expression levels were unchanged. In gelatin zymography analyses, MMP-9 activity in the midbrain gradually increased 12 to 24 h after morphine treatment. Increment in MMP-9 activity in the midbrain was also observed on days 3-5. Our findings suggest that persistent MMP-9 activation observed after the transient increment in MMP-9 expression from the early phase of morphine treatment may contribute to the development of morphine tolerance.
Journal: European Journal of Pharmacology - Volume 683, Issues 1â3, 15 May 2012, Pages 86-92