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https://www.readbyqxmd.com/read/29791710/postoperative-pain-and-analgesia-is-there-a-genetic-basis-to-the-opioid-crisis
#1
Randa K Elmallah, Prem N Ramkumar, Anton Khlopas, Rathika R Ramkumar, Morad Chughtai, Nipun Sodhi, Assem A Sultan, Michael A Mont
BACKGROUND: Multiple factors have been implicated in determining why certain patients have increased postoperative pain, with the potential to develop chronic pain. The purpose of this study was to: 1) identify and describe genes that affect postoperative pain perception and control; 2) address modifiable risk factors that result in epigenetic altered responses to pain; and 3) characterize differences in pain sensitivity and thresholds between opioid-naïve and opioid-dependent patients...
June 1, 2018: Surgical Technology International
https://www.readbyqxmd.com/read/29791013/frontline-science-buprenorphine-decreases-ccl2-mediated-migration-of-cd14-cd16-monocytes
#2
Matias Jaureguiberry-Bravo, Lillie Lopez, Joan W Berman
HIV infection of the CNS causes neuroinflammation and damage that contributes to the development of HIV-associated neurocognitive disorders (HAND) in greater than 50% of HIV-infected individuals, despite antiretroviral therapy (ART). Opioid abuse is a major risk factor for HIV infection. It has been shown that opioids can contribute to increased HIV CNS pathogenesis, in part, by modulating the function of immune cells. HIV enters the CNS within two weeks after peripheral infection by transmigration of infected monocytes across the blood brain barrier (BBB)...
May 23, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29790360/-current-and-future-pharmacotherapy-of-severe-psychiatric-disorders
#3
Eva Češková
Despite of tremendous development in CNS research, current treatment is suboptimal especially in severe mental disorders. In medicine, there are two main methods of improving the healthcare provided: seeking new treatment procedures and perfecting (optimizing) the existing ones. Optimization of treatment includes not only practical tools such as therapeutic drug monitoring, but also implementation of general trends into the clinical practice. New pharmacological options include drugs aimed at other than monoaminergic systems and old drugs used before the psychopharmacological era...
2018: Casopís Lékar̆ů C̆eských
https://www.readbyqxmd.com/read/29790354/-opioids-and-new-trends-in-pain-therapy
#4
Jan Lejčko
Opioids are well known for their ability to reduce the perception of pain without a loss of consciousness. However, the influence of opioids on organism is very complex. Clinical pharmacology of currently available opioid analgesics is determined by three major factors - their opioid receptor properties, pharmacokinetic properties and genetic polymorphism in the opiate receptor and cytochrome P450 isoform. In acute severe pain are opioids very efficient. Long-term experience with opioid analgesia in patients with cancer pain has shown high favorable risk/benefit ratio...
2018: Casopís Lékar̆ů C̆eských
https://www.readbyqxmd.com/read/29788757/expression-of-nmda-receptor-subunits-in-human-blood-lymphocytes-a-peripheral-biomarker-in-online-computer-game-addiction
#5
Mitra-Sadat Sadat-Shirazi, Nasim Vousooghi, Bentolhoda Alizadeh, Seyed Mohammad Makki, Seyed Zeinolabedin Zarei, Shahrzad Nazari, Mohammad Reza Zarrindast
Background and aims Repeated performance of some behaviors such as playing computer games could result in addiction. The NMDA receptor is critically involved in the development of behavioral and drug addictions. It has been claimed that the expression level of neurotransmitter receptors in the brain may be reflected in peripheral blood lymphocytes (PBLs). Methods Here, using a real-time PCR method, we have investigated the mRNA expression of GluN2A, GluN2D, GluN3A, and GluN3B subunits of the NMDA receptor in PBLs of male online computer game addicts (n = 25) in comparison with normal subjects (n = 26)...
May 23, 2018: Journal of Behavioral Addictions
https://www.readbyqxmd.com/read/29785888/the-impact-of-oprm1-s-genetic-polymorphisms-on-methadone-maintenance-treatment-in-opioid-addicts-a-systematic-review
#6
Bilel Oueslati, Olfa Moula, Rim Ghachem
AIM: Methadone is a long-acting opioid receptor agonist. It is prescribed to patients with opioid-related use disorders. The OPRM1 gene encodes for methadone's main receptor. It appears that polymorphisms in OPRM1 may affect the efficacy of methadone maintenance treatment (MMT). OBJECTIVE: Our purpose was to identify all relevant published papers dealing with the impact ofOPRM1's SNPs  on MMT's efficacy and to summarize results in order to evaluate the relevance of conducting pretherapeutic genotyping in opioid addicts prior to the onset of MMT...
May 22, 2018: Pharmacogenomics
https://www.readbyqxmd.com/read/29785554/interactions-between-kappa-and-mu-opioid-receptor-agonists-effects-of-the-ratio-of-drugs-in-mixtures
#7
Vanessa Minervini, Hannah Y Lu, Jahnavi Padarti, Daniela C Osteicoechea, Charles P France
RATIONALE: Pain is the leading reason for seeking health care, and mu opioid receptor agonists continue to be prescribed despite well-documented adverse effects. Kappa opioid receptor agonists have antinociceptive effects with little to no abuse liability and might be useful for treating pain in mixtures. Kappa:mu opioid mixtures might be useful if therapeutic effects of each drug can be selectively increased while reducing or avoiding the adverse effects that occur with larger doses of each drug alone...
May 22, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29782941/dopamine-and-serotonin-metabolism-associated-with-morphine-reward-and-its-inhibition-with-buspirone-a-study-in-the-rat-striatum
#8
Darakhshan Jabeen Haleem, Shazia Nawaz, Tabinda Salman
Adaptations within the nucleus accumbens (NAc) and caudate nucleus (CN) dopamine neurotransmission are involved in behavioral sensitization and enhanced incentive motivation towards drug paired stimuli which lead to drug addiction. Serotonin (5-hydroxytryptamine; 5-HT) can modulate dopamine neurotransmission to reduce rewarding effects of drugs of abuse. A recent study from our laboratory shows that rewarding effects of morphine are inhibited in rats co-treated with buspirone. To understand the neurochemical mechanism involved in morphine addiction and its inhibition with buspirone, present study determines the effects of buspirone, morphine and their co-administration on the metabolism of serotonin and dopamine in the NAc and CN...
May 18, 2018: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29782857/quaternary-ammonium-salt-of-u50-488h-elicits-protective-effects-against-hypoxic-pulmonary-hypertension
#9
Yaguang Zhou, Xin Tian, Xueying Wang, Yuanbo Wang, Rong Fan, Yuemin Wang, Na Feng, Shumiao Zhang, Haitao Guo, Xiaoming Gu, Min Jia, Wen Yin, Zuoxu Hou, Juan Li, Jianming Pei
The present study aimed to investigate the role of quaternary ammonium salt of U50,488H (Q-U50,488H) in hypoxic pulmonary hypertension (HPH) and underlying mechanisms involved. A HPH animal model was established in rats under hypoxia and the mean pulmonary arterial pressure (mPAP) and right ventricular pressure (RVP) were measured. Relaxation of the pulmonary artery in response to Q-U50,488H was determined. In addition, expression and activity of endothelial nitric oxide (NO) synthase (eNOS) and inducible NO synthase (iNOS) with NO content, Akt expression, total antioxidant capacity (T-AOC), and gp91phox were evaluated...
May 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29782380/negative-modulation-of-spinal-%C3%AE%C2%BA-opioid-receptor-mediated-antinociception-by-the-%C3%A2%C2%B5-opioid-receptor-at-selective-doses-of-pentazocine
#10
Douglas L Robinson, Subodh Nag, Sukhbir S Mokha
The mixed-action κ-opioid receptor (KOR) agonist, pentazocine, binds to both KOR and the µ-opioid receptor (MOR). Racemic (±)-pentazocine and (-)-pentazocine, each administered systemically, have been shown to produce antinociception in various animal models. In contrast, racemic (±)-pentazocine failed to produce antinociception when administered intrathecally (i.t.). However, whether spinal activation of KOR and MOR by (-)-pentazocine produces antinociception and the relative contribution of KOR and MOR in mediating antinociception remain unknown...
May 18, 2018: Neuroreport
https://www.readbyqxmd.com/read/29781960/a-peripherally-restricted-cannabinoid-1-receptor-agonist-as-a-novel-analgesic-in-cancer-induced-bone-pain
#11
Hong Zhang, Dominique M Lund, Haley A Ciccone, William D Staatz, Mohab M Ibrahim, Tally M Largent-Milnes, Herbert H Seltzman, Igor Spigelman, Todd W Vanderah
Many malignant cancers, including breast cancer, have a propensity to invade bones, leading to excruciating bone pain. Opioids are the primary analgesics used to alleviate this cancer-induced bone pain (CIBP) but are associated with numerous severe side effects, including enhanced bone degradation, which significantly impairs patients' quality of life. In contrast, agonists activating only peripheral CB1 receptors (CB1Rs) have been shown to effectively alleviate multiple chronic pain conditions with limited side effects, yet no studies have evaluated their role(s) in CIBP...
May 16, 2018: Pain
https://www.readbyqxmd.com/read/29781560/conditioned-reward-of-opioids-but-not-psychostimulants-is-impaired-in-gaba-a-receptor-%C3%AE-subunit-knockout-mice
#12
Milo S Siivonen, Elena de Miguel, Juho Aaltio, Aino K Manner, Mikko Vahermo, Jari Yli-Kauhaluoma, Anni-Maija Linden, Teemu Aitta-Aho, Esa R Korpi
Extrasynaptic δ subunit-containing γ-aminobutyric acid type A receptors (δ-GABAA Rs) are emerging as targets for a number of neuropsychopharmacological drugs, including the direct GABA-site agonist gaboxadol and neuroactive steroids. Among other regions, these δ-GABAA Rs are functionally expressed in the ventral tegmental area (VTA), the cell body region of mesocorticolimbic dopamine (DA) system important for motivated behaviors, and in the target region, the nucleus accumbens. Gaboxadol and neurosteroids induce VTA DA neuron plasticity ex vivo, by inhibiting the VTA GABA neurons, and aversive place conditioning, which are absent in the δ-GABAA R knockout mice (δ-KO)...
May 21, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29780165/a-medial-prefrontal-cortex-nucleus-acumens-corticotropin-releasing-factor-circuitry-for-neuropathic-pain-increased-susceptibility-to-opioid-reward
#13
Yuanzhong Kai, Yanhua Li, Tingting Sun, Weiwei Yin, Yu Mao, Jie Li, Wen Xie, Shi Chen, Likui Wang, Juan Li, Zhi Zhang, Wenjuan Tao
Recent studies have shown that persistent pain facilitates the response to morphine reward. However, the circuit mechanism underlying this process remains ambiguous. In this study, using chronic constriction injury (CCI) of the sciatic nerve in mice, we found that persistent neuropathic pain reduced the minimum number of morphine conditioning sessions required to induce conditioned place preference (CPP) behavior. This dose of morphine had no effect on the pain threshold. In the medial prefrontal cortex (mPFC), which is involved in both pain and emotion processing, corticotropin-releasing factor (CRF) expressing neuronal activity was increased in CCI mice...
May 21, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29780163/heteromerization-of-%C3%AE-opioid-receptor-and-cholecystokinin-b-receptor-through-the-third-transmembrane-domain-of-the-%C3%AE-opioid-receptor-contributes-to-the-anti-opioid-effects-of-cholecystokinin-octapeptide
#14
Yin Yang, Qian Li, Qi-Hua He, Ji-Sheng Han, Li Su, You Wan
Activation of the cholecystokinin type B receptor (CCKBR) by cholecystokinin octapeptide (CCK-8) inhibits opioid analgesia. Chronic opiate treatment leads to an increase in the CCK-8 concentration and thus enhances the antagonism of CCK-8 against opioid analgesia; the underlying molecular mechanisms remain of great interest. In the present study, we validated the colocalization of the μ-opioid receptor (MOR) and CCKBR in pain signal transmission-related spinal cord dorsal horn and dorsal root ganglion neurons of rats...
May 21, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29780077/the-effect-of-remifentanil-on-the-minimum-alveolar-concentration-mac-and-mac-derivatives-of-sevoflurane-in-dogs
#15
Yusuke Murahata, Yoshiaki Hikasa, Sho Hayashi, Koki Shigematsu, Natsuki Akashi, Tomohiro Osaki, Takeshi Tsuka, Yoshiharu Okamoto, Tomohiro Imagawa
Remifentanil is an ultra-short-acting μ-opioid receptor agonist. The purpose of this study was to determine the relationship of the minimum alveolar concentration (MAC) of sevoflurane and other MAC derivatives, including the MAC for blocking adrenergic responses (MAC-BAR) and the MAC at which tracheal extubation is occurred (MAC-extubation), with or without remifentanil infusion. Six healthy adult beagle dogs were randomly anesthetized three times for determining the MAC-BAR (SEVMAC-BAR ), MAC (SEVMAC ), and MAC- extubation (SEVMAC-extubation ) of sevoflurane under infusion of saline and remifentanil at rates of 0...
May 21, 2018: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/29779230/role-of-mu-but-not-delta-or-kappa-opioid-receptors-in-context-induced-reinstatement-of-oxycodone-seeking
#16
Jennifer M Bossert, Jennifer K Hoots, Ida Fredriksson, Sweta Adhikary, Michelle Zhang, Marco Venniro, Yavin Shaham
Relapse to nonmedical use of prescription opioids often occurs after exposure to places previously associated with drug use. Here, we describe a rat model of context-induced reinstatement of oxycodone seeking after repeated cycles of drug self-administration and extinction-induced abstinence. We also determined the role of mu, delta, and kappa opioid receptors (MOR, DOR, KOR) in this reinstatement. We trained rats to self-administer oxycodone for 6 h/d in Context A; lever pressing was paired with a discrete cue...
May 19, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29778745/phytohormone-abscisic-acid-elicits-antinociceptive-effects-in-rats-through-the-activation-of-opioid-and-peroxisome-proliferator-activated-receptors-%C3%AE-%C3%AE
#17
Mahtab Mollashahi, Mehdi Abbasnejad, Saeed Esmaeili-Mahani
The phytohormone abscisic acid exists in animal tissues particularly in the brain. However, its neurophysiological effects have not yet been fully clarified. This study was designed to evaluate the possible antinociceptive effects of abscisic acid on animal models of pain and determine its possible signaling mechanism. Tail-flick, hot-plate and formalin tests were used to assess the nociceptive threshold. All experiments were carried out on male Wistar rats. To determine the role of Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) and opioid receptors on the induction of abscisic acid antinociception, specific antagonists were injected 15min before abscisic acid...
May 17, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29777732/antinociceptive-effect-of-tadalafil-in-various-pain-models-involvement-of-opioid-receptors-and-nitric-oxide-cyclic-gmp-pathways
#18
Mohammad M Mehanna, Souraya Domiati, Hania Nakkash Chmaisse, Ahmed El Mallah
Nitric oxide has been proven to play an important role in nociception, accordingly, its promoters, phosphodiesterase inhibitors have been investigated as pain response modulators. Aiming to evaluate the central effect of tadalafil, a phosphodiesterase 5 inhibitor, and to determine its EC50, tail flick and hot plate tests were utilized. On the other hand, its nociceptive peripheral analgesic effect was assessed through acetic-acid induced writhing model. Formalin test was used to appraise both non-inflammatory and inflammatory pain responses...
May 16, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29776952/activity-based-concept-to-screen-biological-matrices-for-opiates-and-synthetic-opioids
#19
Annelies Cannaert, Lakshmi Vasudevan, Melissa Friscia, Amanda L A Mohr, Sarah M R Wille, Christophe P Stove
BACKGROUND: Detection of new highly potent synthetic opioids is challenging as new compounds enter the market. Here we present a novel screening method for the detection of opiates and (synthetic) opioids based on their activity. METHODS: A cell-based system was set up in which activation of the μ -opioid receptor (MOR) led to recruitment of β-arrestin 2, resulting in functional complementation of a split NanoLuc luciferase and allowing readout via bioluminescence...
May 18, 2018: Clinical Chemistry
https://www.readbyqxmd.com/read/29776484/corticotropin-releasing-factor-in-the-brain-and-blocking-spinal-descending-signals-induce-hyperalgesia-in-the-latent-sensitization-model-of-chronic-pain
#20
Wenling Chen, Yvette Taché, Juan Carlos Marvizón
Latent sensitization is a model of chronic pain in which an injury triggers a period of hyperalgesia followed by an apparent recovery, but in which pain sensitization persists but is suppressed by opioid and adrenergic receptors. One important characteristic of latent sensitization is that hyperalgesia can be triggered by acute stress. To determine whether the effect of stress is mimicked by the activation of corticotropin-releasing factor (CRF) signaling in the brain, rats with latent sensitization induced by injecting complete Freund's adjuvant (CFA, 50 μl) in one hind paw were given an intracerebroventricular (i...
June 15, 2018: Neuroscience
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