Biogenesis of various endogenous opioid peptides, anatomical distribution and the characteristics of multiple receptors with which they interact provides an opportunity for understanding the role of opioid systems and mechanism of opioid tolerance. Cellular and anatomical distribution of opioid receptor and their function is important for identification of neuronal systems and local network inv...

In this article we review recent advances in our understanding of the crucial role of the Regulator of G protein Signaling (RGS) proteins in opioid signaling mechanisms and opioid tolerance development. Opioids exert their physiologic effects via complex G protein-coupled receptor-signaling mechanisms, and RGS proteins are now known to tightly regulate the G protein signaling cycle. RGS protein...

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...

Opioids have been successfully used for the management of acute and cancer-related pain. Concerns regarding side effects, tolerance, dependence, addiction, and hyperalgesia have limited the use of opioids for the management of chronic nonmalignant pain. This article will review updated information from both clinical and preclinical studies regarding opioid-induced hyperalgesia, tolerance, and d...

Diabetes is one of the most common diseases in all societies including Iran. One of its important complications is the neuropathic pain, which can be relieved by opioid drugs such as morphine. Opioid therapy is restricted due to development of tolerance and physical or mental dependence. In this study, the effect of diabetes on morphine analgesia and development of morphine tolerance and depend...

the catastrophic effects of opioids use on public health and the economy are documented clearly in numerous studies. repeated morphine administration can lead to either a decrease (tolerance) or an increase (sensitization) in its behavioral and rewarding effects. morphine-induced sensitization is a major problem and plays an important role in abuse of the opioid drugs. studies reported that mor...

Tolerance, one of several behavioral adaptations to prolonged opioid treatment, has long been explained by desensitization of opioid receptor signaling and loss of surface receptors. However, recent evidence presents an alternative hypothesis, suggesting that receptor internalization could in fact reduce tolerance in vivo.

opium is one of the oldest herbal medicines currently used as an analgesic, sedative and antidiarrheal treatment. the effects of opium are principally mediated by the μ -,κ- and δ-opioid receptors. opioid substances consist of all natural and synthetic alkaloids that are derived from opium. most of their effects on gastrointestinal motility and secretion result from suppression of neural activi...

UNLABELLED Opiate analgesics such as morphine are often used for pain therapy. However, antinociceptive tolerance and dependence may develop with long-term use of these drugs. It was found that μ-opioid receptors can interact with δ-opioid receptors, and morphine antinociceptive tolerance can be reduced by blocking δ-opioid receptors. Recent studies have shown that μ- and δ-opioid receptors are...

This review will introduce the concept of toll-like receptor (TLR)-mediated glial activation as central to all of the following: neuropathic pain, compromised acute opioid analgesia, and unwanted opioid side effects (tolerance, dependence, and reward). Attenuation of glial activation has previously been demonstrated both to alleviate exaggerated pain states induced by experimental pain models a...