• Yue Zhang, Kai Wang, Minyan Lin, Qi Li, and Yanguo Hong.
• Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University, Fuzhou, Fujian 350117, China.
• Eur. J. Pharmacol. 2017 Nov 15; 815: 10-17.

AbstractOpiate tolerance is a critical issue in pain management. Previous studies show that activation of Mas-related gene (Mrg) C receptor can modulate the development of morphine tolerance. This study was designed to investigate the underlying mechanism(s). Intrathecal (i.t.) administration of morphine (20µg) increased the expression of interleukin-1β (IL-1β) and matrix metalloproteinase-9 (MMP-9) in small- and medium-sized neurons in dorsal root ganglia (DRG). Co-administration of bovine adrenal medulla 8-22 (BAM8-22), a selective MrgC receptor agonist, via i.t. route inhibited the increase of IL-1β and MMP-9 in the DRG. Exposure of DRG cultures to morphine (3.3μM) for 3 or 5 days, but not for 1 day, induced an increase in MMP-9 mRNA expression. The treatment with BAM8-22 (10nM) for 20, 40 or 60min abolished chronic (5 days) morphine-induced increase of MMP-9 mRNA in the cultured DRG. The treatment with BAM8-22 for 1h inhibited chronic morphine-induced increase of MMP-9 and IL-1β mRNA in DRG but these effects were abolished by MrgC receptor antibody. The treatment with BAM8-22 for 24 and 72h respectively inhibited and enhanced morphine-induced expression of MMP-9 and IL-1β mRNA in the cultured DRG. The BAM8-22-induced inhibition and enhancement were abolished by MrgC receptor antibody. The results suggest that the inhibition of IL-1β and MMP-9 expressions in DRG underlain the modulation of morphine tolerance by the acute activation of MrgC receptors. The chronic activation of MrgC receptors can facilitate morphine-induced increase of MMP-9 and IL-1β expressions in DRG.Copyright © 2017 Elsevier B.V. All rights reserved.

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