Modulation of morphine-induced antinociception in acute and chronic opioid treatment by ibudilast

Anesthesiology
Tuomas O LiliusEija A Kalso

Abstract

Opioid analgesics are effective in relieving chronic pain, but they have serious adverse effects, including development of tolerance and dependence. Ibudilast, an inhibitor of glial activation and cyclic nucleotide phosphodiesterases, has shown potential in the treatment of neuropathic pain and opioid withdrawal. Because glial cell activation could also be involved in the development of opioid tolerance in rats, the authors studied the antinociceptive effects of ibudilast and morphine in different models of coadministration. Antinociception was assessed using male Sprague- Dawley rats in hot plate and tail-flick tests. The effects of ibudilast on acute morphine-induced antinociception, induction of morphine tolerance, and established morphine tolerance were studied. Systemic ibudilast produced modest dose-related antinociception and decreased locomotor activity at the studied doses of 2.5-22.5 mg/kg. The highest tested dose of 22.5 mg/kg produced 52% of the maximum possible effect in the tail-flick test. It had an additive antinociceptive effect when combined with systemic morphine. Coadministration of ibudilast with morphine did not attenuate the development of morphine tolerance. However, in morphine-tolerant rats, ibudilast ...Continue Reading

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Citations

Jun 1, 2011·British Journal of Anaesthesia·I Power
May 5, 2012·Anesthesia and Analgesia·Tuomas O LiliusEija A Kalso
Dec 12, 2013·CNS Drugs·Leandro Francisco Silva Bastos, Márcio Matos Coelho
Nov 12, 2014·Translational Psychiatry·J L JohnsonM R Hutchinson
Sep 30, 2010·Peptides·Richard J Bodnar
Aug 1, 2013·European Journal of Pain : EJP·T O LiliusE A Kalso
May 27, 2015·The Journal of Pharmacy and Pharmacology·Graciela E EscuderoCarlos H Laino
Dec 23, 2014·European Journal of Pharmacology·Ahmad A Altarifi, S Stevens Negus
Aug 9, 2016·Expert Opinion on Investigational Drugs·Andrew D GoodmanAndrew D Smith
Apr 11, 2017·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Verena E MetzSandra D Comer

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