Involvement of matrix metalloproteinase-9 in the development of morphine tolerance

Kazuo Nakamoto, Shintaro Kawasaki, Takuro Kobori, Wakako Fujita-Hamabe, Hiroyuki Mizoguchi, Kiyofumi Yamada, Toshitaka Nabeshima, Shogo Tokuyama

研究成果: Article査読

31 被引用数 (Scopus)

抄録

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(-/-) 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.

本文言語English
ページ(範囲)86-92
ページ数7
ジャーナルEuropean Journal of Pharmacology
683
1-3
DOI
出版ステータスPublished - 15-05-2012

All Science Journal Classification (ASJC) codes

  • 薬理学

フィンガープリント

「Involvement of matrix metalloproteinase-9 in the development of morphine tolerance」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル