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J Inj Violence Res. 2014 Jul;6(2):72-8. doi: 10.5249/jivr.v6i2.497. Epub 2013 Oct 11.

Role of phosphodiesterase inhibitor Ibudilast in morphine-induced hippocampal injury.

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Department of Anatomy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. E-mail:



Opioid drugs are used in the treatment of acute post-surgical pain and chronic pain, such as those associated with cancer. Opioid used is associated with complications such as analgesic tolerance, dependence and opioid abuse. The molecular mechanisms of unwanted opioid responses are varied but recent advances have highlighted elevations in pro-inflammatory cytokines and pro-inflammatory glial following chronic administration of morphine. In this study we investigated the neurodegenerative effects of morphine through its effects on Toll-Like Receptor 4 (TLR4) in the male rat hippocampus and evaluated the level of Interleukin-1 beta (IL-1β). Then we compared the difference between inhibitory effects on mu opioid receptors (by β-Funaltrexamine, β-FNA) and TLR4 (by Ibudilast). Subsequently, we assessed the amount of IL-1β and the number of granular cells in male rat hippocampus.


Adult male rats (n=24) were treated with sucrose, morphine, Ibudilast (7.5 mg/kg) and β-FNA (20 mg/kg) for 30 days. Their brains were isolated and hemisected with one hippocampus for granular cell and the other used for IL-1 β immunoblotting.


Data showed that Ibudilast suppresses IL-1 β expression significantly more than β-FNA. The granular cell count displayed significant differences.


Our results suggested that Ibudilast can be used for controlling and treatment of morphine-induced CNS inflammations or traumatic conditions.

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