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

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)86-92
Number of pages7
JournalEuropean Journal of Pharmacology
Volume683
Issue number1-3
DOIs
Publication statusPublished - 15-05-2012
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 9
Morphine
Matrix Metalloproteinase Inhibitors
Mesencephalon
Therapeutics
Neuronal Plasticity
Neuralgia
Gelatin
Tail
Spinal Cord
Proteins

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Nakamoto, K., Kawasaki, S., Kobori, T., Fujita-Hamabe, W., Mizoguchi, H., Yamada, K., ... Tokuyama, S. (2012). Involvement of matrix metalloproteinase-9 in the development of morphine tolerance. European Journal of Pharmacology, 683(1-3), 86-92. https://doi.org/10.1016/j.ejphar.2012.03.006
Nakamoto, Kazuo ; Kawasaki, Shintaro ; Kobori, Takuro ; Fujita-Hamabe, Wakako ; Mizoguchi, Hiroyuki ; Yamada, Kiyofumi ; Nabeshima, Toshitaka ; Tokuyama, Shogo. / Involvement of matrix metalloproteinase-9 in the development of morphine tolerance. In: European Journal of Pharmacology. 2012 ; Vol. 683, No. 1-3. pp. 86-92.
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Nakamoto, K, Kawasaki, S, Kobori, T, Fujita-Hamabe, W, Mizoguchi, H, Yamada, K, Nabeshima, T & Tokuyama, S 2012, 'Involvement of matrix metalloproteinase-9 in the development of morphine tolerance', European Journal of Pharmacology, vol. 683, no. 1-3, pp. 86-92. https://doi.org/10.1016/j.ejphar.2012.03.006

Involvement of matrix metalloproteinase-9 in the development of morphine tolerance. / Nakamoto, Kazuo; Kawasaki, Shintaro; Kobori, Takuro; Fujita-Hamabe, Wakako; Mizoguchi, Hiroyuki; Yamada, Kiyofumi; Nabeshima, Toshitaka; Tokuyama, Shogo.

In: European Journal of Pharmacology, Vol. 683, No. 1-3, 15.05.2012, p. 86-92.

Research output: Contribution to journalArticle

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Nakamoto K, Kawasaki S, Kobori T, Fujita-Hamabe W, Mizoguchi H, Yamada K et al. Involvement of matrix metalloproteinase-9 in the development of morphine tolerance. European Journal of Pharmacology. 2012 May 15;683(1-3):86-92. https://doi.org/10.1016/j.ejphar.2012.03.006