Functionally selective signaling appears to contribute to the variability in mechanisms that underlie tolerance to the antinociceptive effects of opioids. The present study tested this hypothesis by examining the contribution of G protein-coupled receptor kinase (GRK)/Protein kinase C (PKC) and C-Jun N-terminal kinase (JNK) activation on both the expression and development of tolerance to morph...

μ-Opioid receptor desensitization is considered an initial step in the development of tolerance. Curiously, the commonly used opioid morphine produces robust tolerance but minimal acute desensitization. This study was designed to test the hypothesis that desensitization is indeed present in morphine-treated animals and is distinguished from cellular tolerance by time course of recovery and mech...

Introduction: Stress inhibits the development of tolerance to morphine analgesia via activating Hypothalamic- Pituitary-Adrenal (HPA) axis. Modified catecholamine systems have been reported following morphine tolerance development. In the current study we tried to evaluate changes in the gene expression levels for MAO-A, MAO-B, COMT and thyrosine hydroxylase (TyH) enzymes following chronic p...

Repeated administration of morphine is associated with tolerance to its antinociceptive properties. However, constipation remains the major side effect of chronic exposure to morphine. In contrast, previous studies suggest that tolerance to opioids develops in the ileum of several species. In this study, we provide evidence that constipation may arise due to a lack of tolerance development to m...

Morphine is an effective analgesic in clinical practice; however, its long-term administration causes tolerance, thereby limiting its use. The development of opioid tolerance and its associated hyperalgesia has been associated with interactions between opioid receptors and excitatory amino acids or cytokines. Targeted inhibition of excitatory amino acidand cytokine-mediated signaling pathways m...

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 ...

Tolerance to morphine analgesia following repeated administration disturbs the continuation of opioid therapy for severe pain. Emerging evidence suggests that the development of morphine tolerance may be antagonized by painful stimuli. To clarify the detailed mechanisms of these phenomena, we examined the effects of several pain stimuli on morphine-induced tolerance. Subcutaneous (s.c.) injecti...

The role of glutamate receptors within the nucleus accumbens in morphine tolerance has been postulated. Previous studies have reported that glutamate receptors exert their effects in part through the release of nitric oxide (NO). In the present study, the effect of intra-accumbal injections of L-arginine, the NO precursor and L-NAME, the NOS inhibitor on the morphine tolerance in Wistar rats (2...

Introduction: Ultra low dose (ULD) morphine induces hyperalgesia which is mediated by excitatory Gscoupled opioid receptors. This study was designed to investigate the development of tolerance to hyperalgesic effect of morphine. Also we attempt to seek possible similarity, in view of Gs proteins, between hyperalgesic effect of ULD and hyperalgesic effect after tolerance to HD. Method: Male ...

caffeine, an adenosine a1, a2a, and a2b receptor antagonist, is frequently used as an adjuvant analgesic in combination with non steroidal anti-inflammatory drugs or opioids. the aim of this study was to evaluate the effects of caffeine on preventing the development of morphine tolerance and analgesia in mice. in this study, different groups of mice received morphine (30 mg/kg) + saline (10 ml/...