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Med Hypotheses. 2012 Jan;78(1):102-6. doi: 10.1016/j.mehy.2011.10.003. Epub 2011 Nov 1.

The role of cyclo-oxygenase inhibitors in attenuating opioid-induced tolerance, hyperalgesia, and dependence.

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Department of Physiology, Molecular and Cell Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.


There is no denying that opioids are the most important analgesic drugs which are widely used in clinical situations. Still, prolonged administration of these drugs can cause to reduce their analgesic efficacy due to the development of tolerance. These drugs can also cause induction of hyperalgesia. In addition, long-term administration of opioids through reinforcing- and rewarding pathways of limbic system can result in expression of opioid dependence with the unintended consequences of opioid abuse/misuse and finally opioid addiction. As studies show, over-activity in cyclo-oxygenase pathways and production of prostaglandins due to long-term exposures of opioid have a critical role in the development of tolerance to antinociceptive effect of opioid, hyperalgesia, and opioid dependence. The present study aims at suggesting the hypothesis that through blending a non-steroid anti-inflammatory drug with opioid actively causes reduction in unwanted effects of opioid i.e. by inhibition of opioid-induced cyclo-oxygenase overactivity whereas it is well-known that the combination therapy via reducing opioid dosage reduces the unwanted effects.

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