the parafascicular nucleus (pfn) of thalamus, as a supraspinal structure, has an important role in processing of nociceptive information. in addition, μ-opioid receptor contributes to supraspinal modulation of nociception. in the present study, the effects of microinjection of naloxone (a non-specific opioid-receptor antagonist) and naloxonazine (a specific μ-opioid receptor antagonist) were in...

PURPOSE OF REVIEW Recent studies highlighting between-opioid differences in patient outcomes, opioid receptor interactions and animal study findings implicating a 'fine control' mechanism underpinning potential diversity in opioid receptor signalling that could potentially be exploited to develop novel opioid analgesics with improved tolerability are reviewed. RECENT FINDINGS Recent clinical ...

BACKGROUND Opiates such as morphine are the most powerful analgesics, but their protracted use is restrained by the development of tolerance to analgesic effects. Recent works suggest that tolerance to morphine might be due to its inability to promote mu opioid receptor endocytosis, and the co-injection of morphine with a mu opioid receptor internalizing agonist like [D-Ala(2),N-Me-Phe(4),Gly-o...

Exposure to opiates such as morphine can lead to psychological and physical dependence in both adult and infant humans. Infant rats experience opiate withdrawal behaviors that are qualitatively different from the withdrawal behaviors displayed by adult rats. In the adult, withdrawal is largely mediated by the mu-opioid receptor. We sought to understand more about what role each opioid receptor ...

The transient receptor potential vanilloid-1 (TRPV1) receptor is involved in peripheral and spinal nociceptive processing and is a therapeutic target for pain. We have shown previously that TRPV1 in the ventrolateral periaqueductal gray (VL-PAG) tonically contributes to brain stem descending antinociception by stimulating glutamate release into the rostral ventromedial medulla and off neuron ac...

Opioids are the most potent analgesics. However, their clinical use is limited by side effects like respiratory depression and their high potential for abuse. In addition, they modulate immune functions and cause immunosuppression. Effects of clinically important opioids like morphine are mediated by the mu-opioid receptor. Knowledge about the mechanisms controling the expression of the mu-opio...

Opioid receptor binding, including the mu, delta, and kappa receptor subtypes, was compared in morphine-injected and control rats. Brain tissues were homogenized and centrifuged either one or two times prior to receptor binding assay. In brain membranes from morphine-injected rats centrifuged once, there was a decrease in mu, but not delta or kappa, binding compared to controls, perhaps indicat...

Compound trans-4-(p-bromophenyl)-4-(dimethylamino)-1-(2-thiophen-2-yl-ethyl)-cyclohexanol (C8813), structurally unrelated to morphine, is a novel analgesic. The present study examined the antinociception, opioid receptor selectivity and in vitro activity of C8813. The antinociceptive activity was evaluated using mouse hot plate and acetic acid writhing tests. In mouse hot plate test, the antino...

This study was to identify specific regions in kappa opioid receptors that accounted for binding selectivity of kappa ligands. Six chimeric mu/kappa receptors were constructed from cloned rat kappa and mu opioid receptors and transiently expressed in COS-1 cells. All six chimeric mu/kappa receptors bound [3H] diprenorphine with high affinities, indicating that these chimeras retain opioid recep...

Activation of G protein-coupled receptors (GPCRs) may bring about their disappearance from the cell membrane, and it is commonly accepted that G protein-coupled receptor kinases (GRKs) play a key function in this mechanism. Opioid receptors belong to the family of GPCRs and are substrates of GRKs. We examined the fate of delta- and mu-opioid receptors and GRK2 and 3 in living cells during the p...