objective(s): we aimed to examine association of gene expression of mor1 and glun1 at mrna level in the lumbosacral cord and midbrain with morphine tolerance in male wistar rats. materials and methods: analgesic effects of morphine administrated intraperitoneally at doses of 0.1, 1, 5 and 10 mg/kg were examined using a hot plate test in rats with and without a history of 15 days morphine (10 mg...

Respiratory depression is the major cause of death in opioid overdose. We have previously shown that prolonged treatment of mice with morphine induces profound tolerance to the respiratory-depressant effects of the drug (Hill et al., 2016). The aim of the present study was to investigate whether tolerance to opioid-induced respiratory depression is mediated by protein kinase C (PKC) and/or c-Ju...

Opioids, the wonderful analgesics, remain the mainstay in the clinical management of moderate to severe pain. However, development of analgesic tolerance and increase in pain sensitivity are some of the major concerns following opioid treatment. Studies suggest that NMDA receptor-mediated intracellular events play a role in mediating these effects. Moreover, NMDA receptor antagonists effectivel...

Opioid dose escalation or analgesic tolerance is observed during longer treatments in a significant number of patients with chronic pain owing to cancer or nonmalignant tissue injury. Higher doses of morphine are more likely to result in subsensitivity to the drug and worsened quality of life (QOL) by exerting other side effects. Many investigators have been studying the molecular and cellular ...

Repeated injection of opioid analgesics can lead to a progressive loss of effect. This phenomenon is known as tolerance. Several lines of investigations have shown that systemic, intraperitoneal administration or the microinjection of non-opioid analgesics, non-steroidal anti-inflammatory drugs (NSAIDs) into the midbrain periaqueductal gray matter induces antinociception with some effects of to...

Previous studies from our laboratory and others have implicated a critical role of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in opioid tolerance and dependence. Translational research targeting the CaMKII pathway is challenging, if not impossible, because of a lack of selective inhibitors. We discovered in a preliminary study that haloperidol, a butyrophenone antipsychotic drug, in...

In the present study, the contribution of pertussis toxin (PTX)-sensitive G(i/o)-proteins to opioid tolerance and mu-opioid receptor down-regulation in the mouse were examined. Mice were injected once intracerebroventricularly and intrathecally with PTX (0.1 microg/site). Controls were treated with saline. On the 10th day following PTX treatment, continuous subcutaneous infusion of etorphine (1...

BACKGROUND Opiates such as morphine are the most powerful analgesics, but their protracted use is restrained by the development of tolerance to analgesic effects. Recent works suggest that tolerance to morphine might be due to its inability to promote mu opioid receptor endocytosis, and the co-injection of morphine with a mu opioid receptor internalizing agonist like [D-Ala(2),N-Me-Phe(4),Gly-o...

Opioid tolerance and opioid-induced hyperalgesia are conditions that negatively affect pain management. Tolerance is defined as a state of adaptation in which exposure to a drug induces changes that result in a decrease of the drug's effects over time. Opioid-induced hyperalgesia occurs when prolonged administration of opioids results in a paradoxic increase in atypical pain that appears to be ...