background calcium/calmodulin-dependent protein kinase iiα (camkiiα) may modulate the function of mu-opioid receptors by phosphorylation and therefore, be involved in development of morphine-induced analgesic tolerance. objectives the current study aimed to examine changes in gene expression of camkiiα in the lumbosacral cord and midbrain during induction of morphine analgesic tolerance. materi...

Cyclosporine, beside its immunosuppressive action, has several effects on different neuronal functions, such as modulation of neurotransmitter release, the inhibition of nitric oxide synthesis and release, the reduction of cAMP production and inhibition of morphine-induced tolerance. In the present study, the effect of cyclosporine on the expression and development of tolerance to WIN 55,212-2,...

The mechanisms underlying opioid tolerance are not fully understood, but appear to be comprised of two types of plasticity or counter-adaptation, at the cellular level and through neuronal circuits. Current studies mostly emphasize the cellular adaptation mechanisms, which include altered gene expression and receptor desensitization due to phosphorylation and endocytosis. However, the mechanism...

Clinical usage of cannabinoids in chronic pain states is limited by their central side effects and the pharmacodynamic tolerance that sets in after repeated dosage. Analgesic tolerance to cannabinoids in vivo could be caused by agonist-induced downregulation and intracellular trafficking of cannabinoid receptors, but little is known about the molecular mechanisms involved. We show here that the...

beta-Carboline-3-carboxylic acid ethyl ester (beta-CCE) dose-dependently potentiated psychological-stress induced analgesia (PSY-SIA), and the effect was reversed by diazepam. Concurrent exposure to PSY stress or concomitant treatment with beta-CCE blocked the development of analgesic tolerance to morphine; the effect of PSY stress was antagonized by diazepam, and that of beta-CCE was reversed ...

It has been reported that morphine tolerance does not develop in the presence of chronic pain. Therefore, this study was conducted to find out whether chronic inflammatory pain is able to eliminate or attenuate the developed tolerance to analgesic effect of morphine and also to investigate the role of lumbar spinal cord as a candidate site for this interaction. Tolerance was induced in adult ma...

Efficient repetitive clinical use of morphine is limited by its numerous side effects, whereas analgesic tolerance necessitates subsequent increases in dose to achieve adequate levels analgesia. While many studies focused on tolerance, the effect dosing non-analgesic effects has been overlooked. This study aimed characterize morphine-induced behavior and development progression behavioral toler...