Chronic use of opioid analgesics has been hindered by the development of opioid addiction and tolerance. We have reported that curcumin, a natural flavonoid from the rhizome of Curcuma longa, attenuated opioid tolerance, although the underlying mechanism remains unclear. In this study, we tested the hypothesis that curcumin may inhibit Ca/calmodulin-dependent protein kinase II a (CaMKIIa), a pr...

Differences in the mechanisms underlying tolerance and mu-opioid receptor desensitization resulting from exposure to opioid agonists of different efficacy have been suggested previously. The objective of this study was to determine the effects of protein kinase C (PKC) and G protein-coupled receptor kinase (GRK) inhibition on antinociceptive tolerance in vivo to opioid agonists of different eff...

Regulation of the mu-opioid receptor gene by opioid analgesic drugs has not been observed in rats and mice following in vivo treatments that produce tolerance. Although in vivo heterologous regulation of mu-opioid receptor mRNA by non-opioid compounds has been reported, the failure to observe changes in mu-opioid receptor mRNA levels in vivo after treatment with opioid agonists raised the possi...

Opioid and non-opioid mechanisms of analgesia elicited by two kinds of footshock stress that differ only in temporal characteristics previously have been inferred on the basis of susceptibility to naloxone blockade. The present study sought further evidence on this point by comparing these two kinds of footshock analgesia for possible tolerance development and cross-tolerance with morphine. It ...

We have previously reported that stress analgesia sensitive to and insensitive to opiate antagonists can be differentially produced in rats by varying the severity or temporal pattern of inescapable footshock. In these studies, we give further evidence for the opioid and non-opioid bases of these paradigms of stress analgesia. We find that naloxone-sensitive analgesia demonstrates tolerance wit...

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...

To the Editor: We thank Kim et al. for their recent work examining the effect of intraoperative remifentanil on postoperative analgesia in children.1 Certainly, the pharmacokinetic profile of this potent opioid is attractive in modern anesthetic practice, and a thorough understanding of the principles behind tolerance, hyperalgesia, and withdrawal of remifentanil are critical for its safe admin...

Ultra-low-dose opioid antagonists, when combined with opiates, increase the analgesic efficacy and duration of analgesia of the opiate. This enhanced and prolonged analgesia was recently demonstrated in a 350-patient Phase II clinical trial of Oxytrex, a novel drug candidate that combines oxycodone with an ultra-low dose of the opioid antagonist naltrexone. Extensive preclinical data also show ...

BACKGROUND The pivotal role of glial activation and up-regulated inflammatory mediators in the opioid tolerance has been confirmed in rodents but not yet in humans. Here, the authors investigated the intraspinal cytokine and chemokine profiles of opioid-tolerant cancer patients; and to determine if up-regulated chemokines could modify opioid tolerance in rats. METHODS Cerebrospinal fluid samp...

Anesthesiology, V 124 • No 2 483 February 2016 O PIOIDS are highly effective analgesics and as such form the mainstay of pain management after surgery. However, they are associated with a formidable array of side effects, some of them potentially lethal. Also, the opioid signaling system has a remarkable ability—possibly unequaled by any other receptor system...