Antagonists of the NMDA type of excitatory amino acid (EAA) receptor attenuate or reverse the development of tolerance to the analgesic effects of the mu opioid agonist morphine, the delta-1 opioid agonist DPDPE but not the kappa-1 agonist U50,488H or the kappa-3 agonist naloxone benzoylhydrazone. The role of the AMPA subtype of EAA receptor in analgesic tolerance was examined using LY293558, a...

Introduction: In order to study the alterations of beta 1 and 2 integrins mRNA level in rat lumbar spinal cord following the induction of chronic pain and its effect on the development of tolerance to morphine analgesia, we examined the level of expression of these genes in the presence of chronic pain, which is an inhibitor of morphine tolerance. We used induction of chronic pain alone and in ...

OBJECTIVES 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/k...

Identification of adaptations to chronic morphine that are causally associated with opioid tolerance formation has long been intensely pursued by the opioid research community. There is an impressive array of components of signaling pathways that are influenced by chronic opioid administration. This underscores the importance to tolerance mechanisms of the complex interplay of cellular adaptati...

Four experiments were concerned with the development in rats of context-specific tolerance to the sedating and analgesic effects of morphine. Experiment 1 was conducted to assess the temporal course of activity changes and analgesia consequent to acute morphine administration. Experiments 2, 3, and 4 were conducted to assess the development of context-specific morphine tolerance in the two meas...

Cancer pain is caused by continuous tissue injury, which may be due to surgery, infiltration of the surrounding organs including nerves, as well as from mucositis after chemoor radiotherapy. Nerve involvement, chronic opioid therapy and continuous nociceptive input cause hyperalgesia. Chronic stimulation of the dorsal root neurons leads to hyperalgesia and resistance (tolerance) to μ opioid ana...

The effects of ondansetron, a highly potent and selective 5-HT3 receptor antagonist, in the prevention of tolerance to and dependence on morphine were studied in mice using a 9-day schedule. Chronic administration of morphine (10 mg/kg i.p. twice daily for 9 days) produced tolerance to the analgesic effects and animals showed withdrawal jumps on day 10 when challenged with naloxone (2 mg/kg). C...

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 ...

The utility of morphine for the treatment of chronic pain is hindered by the development of tolerance to the analgesic effects of the drug. Morphine is unique among opiates in its ability to activate the mu opioid receptor (MOR) without promoting its desensitization and endocytosis. Here we demonstrate that [D-Ala(2)-MePhe(4)-Gly(5)-ol] enkephalin (DAMGO) can facilitate the ability of morphine ...