Pain associated-anxiety induced by formalin, which resulted in a significant delay in the development of tolerance to morphine antinociception, failed to prevent the development of physical dependence as evidenced by naloxone challenge. Dependence also developed in mice rendered tolerant to morphine. Thus, the development of morphine dependence was observed in the absence and presence of tolera...

It has been shown that stress and chronic pain could prevent the development of tolerance to morphine analgesia, which appears to be related to the activation of hypothalamus–pitutitary–adrenal (HPA) axis, activation of neuroendocrine systems and changes in neurochemical levels. Moreover, the involvement of nitric oxide (NO) in the development of tolerance to morphine analgesia has been implica...

Background and Objective: Today, opioids are used to control and relieve acute and chronic pain. However, the incidence of both tolerance and dependence phenomena for these drugs is a major problem. So, in this study, the combination effect of haloperidol and methadone on the acquisition and expression of morphine dependence and tolerance was examined.    Materials and Methods: Ninety-eight mic...

It has been shown that stress and chronic pain could prevent the development of tolerance to morphine analgesia, which appears to be related to the activation of hypothalamus–pitutitary–adrenal (HPA) axis, activation of neuroendocrine systems and changes in neurochemical levels. Moreover, the involvement of nitric oxide (NO) in the development of tolerance to morphine analgesia has been implica...

Morphine tolerance is a clinical challenge in pain management. Emerging evidence suggests that microRNA (miRNA) plays a regulatory role in the development of morphine tolerance. miR-219-5p (miR-219) targets calmodulin-dependent protein kinase II γ (CaMKIIγ) to activate central pain sensitization via N-methyl-D-aspartate (NMDA) receptor. Therefore, we hypothesized that miR-219-5p attenuates morp...

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...

β-Arrestin2 has been reported to play an essential role in analgesic tolerance. Analgesic tolerance without concomitant tolerance to constipation is a limiting side effect of chronic morphine treatment. Because tolerance to morphine develops in the mouse ileum but not the colon, we therefore examined whether the role of β-arrestin2 in the mechanism of morphine tolerance differs in the ileum and...

Introduction: There is some evidence supporting the reduced activity of integrins following chronic administration of morphine. This reduction might play a role in morphine tolerance development. Manganese binds to the extracellular domain of integrins and makes them to be activated. The effect of integrins activation using manganese on tolerance development to the analgesic effect of morphine ...

UNLABELLED Systemic administration of morphine typically produces greater tolerance than higher efficacy mu-opioid receptor (MOPr) agonists such as fentanyl. The objective of the present study was to test this relationship by measuring antinociceptive efficacy and tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray (vlPAG). MOPr agonist efficacy was evalu...

Tolerance to the analgesic effects of opioids occurs after their chronic administration, a pharmacological phenomenon that has been associated with the development of abnormal pain sensitivity such as hyperalgesia. In the present study, we investigated the role of TRPV1, which is crucial for the transduction of noxious chemical and thermal stimuli, in morphine tolerance and tolerance-associated...