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https://www.readbyqxmd.com/read/29928964/spinal-interleukin-10-produces-antinociception-in-neuropathy-through-microglial-%C3%AE-endorphin-expression-separated-from-antineuroinflammation
#1
Hai-Yun Wu, Xiao-Fang Mao, Xue-Qi Tang, Usman Ali, Evhy Apryani, Hao Liu, Xin-Yan Li, Yong-Xiang Wang
Interleukin 10 (IL-10) is antinociceptive in various animal models of pain without induction of tolerance, and its mechanism of action was generally believed to be mediated by inhibition of neuroinflammation. Here we reported that intrathecal IL-10 injection dose dependently attenuated mechanical allodynia and thermal hyperalgesiain male and female neuropathic rats, with ED50 values of 40.8 ng and 24 ng, and Emax values of 61.5% MPE and 100% MPE in male rats. Treatment with IL-10 specifically increased expression of the β-endorphin (but not prodynorphin) gene and protein in primary cultures of spinal microglia but not in astrocytes or neurons...
June 18, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29928219/acute-opioid-induced-myoclonic-reaction-after-use-of-fentanyl-as-an-anesthetic-drug-for-an-emergency-cesarean-section
#2
Dana Khaled Almedallah, Dana Yousef Alshamlan, Erum Mubbashir Shariff
Myoclonus is an abnormal involuntary movement that has been previously reported with administration of high doses of opioids for prolonged periods of time. In this case, however, we report an acute myoclonic reaction and review the literature on the possible causative pathophysiology. We report the case of a 24-year-old woman who was admitted for postdated cesarean section. She started to have abnormal involuntary movements after administration of an epidural anesthesia containing 700 μg of fentanyl with 115 mL (0...
May 2018: Case Reports in Neurology
https://www.readbyqxmd.com/read/29927768/an-update-on-the-basic-and-clinical-science-of-ketamine-analgesia
#3
Lisa V Doan, Jing Wang
OBJECTIVE: In the context of the current opioid epidemic, there has been a renewed interest in the use of ketamine as an analgesic agent. METHODS: We have reviewed ketamine analgesia. RESULTS: Ketamine is well-known as an antagonist for N-methyl-D-aspartate receptors. In addition, it can regulate the function of opioid receptors and sodium channels. Ketamine also increases signaling through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors...
June 20, 2018: Clinical Journal of Pain
https://www.readbyqxmd.com/read/29927325/inflammation-associated-changes-in-dor-expression-and-function-in-the-mouse-colon
#4
Jesse J DiCello, Ayame Saito, Pradeep Rajasekhar, Emily M Eriksson, Rachel M McQuade, Cameron J Nowell, Benjamin W Sebastian, Jakub Fichna, Nicholas A Veldhuis, Meritxell Canals, Nigel W Bunnett, Simona Elisa Carbone, Daniel P Poole
Endogenous opioids activate opioid receptors (ORs) in the enteric nervous system to control intestinal motility and secretion. The mu OR mediates the deleterious side effects of opioid analgesics, including constipation, respiratory depression and addiction. Although the delta OR (DOR) is a promising target for analgesia, the function and regulation of DOR in the colon are poorly understood. This study provides evidence that endogenous opioids activate DOR in myenteric neurons which may regulate colonic motility...
June 21, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29926144/lappaconitine-a-c18-diterpenoid-alkaloid-exhibits-antihypersensitivity-in-chronic-pain-through-stimulation-of-spinal-dynorphin-a-expression
#5
Ming-Li Sun, Jun-Ping Ao, Yi-Rui Wang, Qian Huang, Teng-Fei Li, Xin-Yan Li, Yong-Xiang Wang
Lappaconitine is a representative C18-diterpenoid alkaloid extracted from Aconitum sinomontanum Nakai and has been prescribed as a pain relief medicine in China for more than 30 years. This study evaluated its antihypersensitivity activity in the rat models of neuropathic and cancer pains and explored its underlying mechanisms. Subcutaneous injection of cumulative doses of lappaconitine produced dose-dependent mechanical antiallodynia and thermal antihyperalgesia in spinal nerve ligation-induced neuropathic rats...
June 20, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29925858/downregulation-of-the-neuronal-opioid-gene-expression-concomitantly-with-neuronal-decline-in-dorsolateral-prefrontal-cortex-of-human-alcoholics
#6
Igor Bazov, Daniil Sarkisyan, Olga Kononenko, Hiroyuki Watanabe, Victor M Karpyak, Tatiana Yakovleva, Georgy Bakalkin
Molecular changes in cortical areas of addicted brain may underlie cognitive impairment and loss of control over intake of addictive substances and alcohol. Prodynorphin (PDYN) gives rise to dynorphin (DYNs) opioid peptides which target kappa-opioid receptor (KOR). DYNs mediate alcohol-induced impairment of learning and memory, while KOR antagonists block excessive, compulsive-like drug and alcohol self-administration in animal models. In human brain, the DYN/KOR system may undergo adaptive changes, which along with neuronal loss, may contribute to alcohol-associated cognitive deficit...
June 20, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29922742/biased-agonism-the-quest-for-the-analgesic-holy-grail
#7
M Alexander Stanczyk, Ram Kandasamy
Opioids alleviate pain, but adverse effects severely limit their usefulness. To solve this problem, biased ligands favoring 1 signaling pathway downstream of the μ-opioid receptor over another are being developed. In the target article, the authors synthesize compounds that preferentially activate G-protein or β-arrestin signaling. They find that increased bias towards G-protein signaling produces better antinociception with minimal side effects in mice models. G-protein-biased opioids may provide a safer treatment strategy...
May 2018: Pain Reports (Baltimore, Md.)
https://www.readbyqxmd.com/read/29922083/ferulic-acid-dimer-as-a-non-opioid-therapeutic-for-acute-pain
#8
Alaini Priebe, Megan Hunke, Raquel Tonello, Yogesh Sonawane, Temugin Berta, Amarnath Natarajan, Nattamai Bhuvanesh, Mahesh Pattabiraman, Surabhi Chandra
Purpose: Search for alternate pain medications has gained more importance in the past few years due to adverse effects associated with currently prescribed drugs including nervous system dysfunction with opioids, gastrointestinal discomfort with nonsteroidal anti-inflammatory drugs, and cardiovascular anomalies with cyclooxygenase-2 (COX-2) inhibitors. Phytomedicine has been explored for the treatment of pain, as these have been used for generations in regional communities and tend to lack major side effects in general...
2018: Journal of Pain Research
https://www.readbyqxmd.com/read/29921657/oligomerization-of-mrgc11-and-%C3%AE-opioid-receptors-in-sensory-neurons-enhances-morphine-analgesia
#9
Shao-Qiu He, Qian Xu, Vinod Tiwari, Fei Yang, Michael Anderson, Zhiyong Chen, Shaness A Grenald, Srinivasa N Raja, Xinzhong Dong, Yun Guan
The μ-opioid receptor (MOR) agonist morphine is commonly used for pain management, but it has severe adverse effects and produces analgesic tolerance. Thus, alternative ways of stimulating MOR activity are needed. We found that MrgC11, a sensory neuron-specific G protein-coupled receptor, may form heteromeric complexes with MOR. Peptide-mediated activation of MrgC11 enhanced MOR recycling by inducing coendocytosis and sorting of MOR for membrane reinsertion. MrgC11 activation also inhibited the coupling of MOR to β-arrestin-2 and enhanced the morphine-dependent inhibition of cAMP production...
June 19, 2018: Science Signaling
https://www.readbyqxmd.com/read/29921501/tapentadol-a-representative-of-a-new-class-of-mor-nri-analgesics
#10
REVIEW
Renata Zajączkowska, Barbara Przewłocka, Magdalena Kocot-Kępska, Joanna Mika, Wojciech Leppert, Jerzy Wordliczek
Tapentadol is a centrally acting analgesic with a dual mode of action as a μ-opioid receptor (MOR) agonist and a noradrenaline reuptake inhibitor (NRI). It was initially approved by the US Food and Drug Administration in November 2008 for the treatment of moderate-to-severe acute pain in adult patients, and in August 2011, for chronic pain in an prolonged release form in the same population. Due to its limited protein binding capacity, the absence of active metabolites and significant microsomal enzyme induction or inhibition, tapentadol has a limited potential for drug-drug interactions...
January 31, 2018: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29917231/itch-and-psyche-psychiatric-aspects-of-pruritus
#11
REVIEW
Mohammad Jafferany, Maryam E Davari
Itch, also referred to as pruritus, is an unpleasant cutaneous sensation provoking the desire to scratch. It is often an uncomfortable, subjective sensation responsible for decreased quality of life in a variety of psychodermatological conditions. Comorbid psychiatric conditions, including depression and anxiety, are frequently associated with itch and scratch cycle. The reciprocal and intricate relationship between the psyche and itch has been widely studied. The neurobiology of itch involves the complexity of specific mediators, itch-related neuronal pathways, and central processing of itch...
June 19, 2018: International Journal of Dermatology
https://www.readbyqxmd.com/read/29916277/efficacy-of-d-l-methadone-in-the-treatment-of-glioblastoma-in-vitro
#12
Konstantin Brawanski, Gero Brockhoff, Peter Hau, Arabel Vollmann-Zwerenz, Christian Freyschlag, Annette Lohmeier, Markus J Riemenschneider, Claudius Thomé, Alexander Brawanski, Martin A Proescholdt
AIM: Recently, D,L-methadone has been put forward as adjuvant treatment in glioblastoma (GBM). METHODS: We analyzed the μ-opioid receptor expression in a set of GBM cell lines and investigated the efficacy of D,L-methadone alone and in combination with temozolomide (TMZ). Results & conclusion: Expression of the μ-opioid receptor was similar in the tested cell lines. High concentrations of D,L-methadone induced apoptosis in all cell lines and showed treatment interaction with TMZ...
June 19, 2018: CNS Oncology
https://www.readbyqxmd.com/read/29916183/modulation-of-mir-139-5p-on-chronic-morphine-induced-naloxone-precipitated-camp-overshoot-in-vitro
#13
Dan-Ni Cao, Jing-Jing Shi, Ning Wu, Jin Li
Chronic exposure to morphine can produce tolerance, dependence and addiction, but the underlying neurobiological basis is still incompletely understood. c-Jun, as an important component of the activator protein-1 transcription factor, is supposed to take part in regulating gene expression in AC/cAMP/PKA signaling. MicroRNA (miRNA) has emerged as a critical regulator of neuronal functions. Although a number of miRNAs have been reported to regulate the μ-opioid receptor expression, there has been no report about miRNAs to regulate chronic morphine-induced, naloxone-precipitated cAMP overshoot...
June 18, 2018: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29916050/opioid-analgesic-drugs-and-serotonin-toxicity-syndrome-mechanisms-animal-models-and-links-to-clinical-effects
#14
REVIEW
Brian A Baldo
Drugs may cause serotonin toxicity by a number of different mechanisms including inhibition of serotonin uptake and metabolism, increased serotonin synthesis and release, activation of serotonin receptors, and inhibition of cytochrome P450 oxidases. Some drug interactions involving opioids can increase intrasynaptic levels of serotonin, and opioid analgesic drugs are now recognized as being involved in some cases of serotonin toxicity especially if administered in conjunction with other serotonergic medications including monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants...
June 18, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29914002/pain-sensitivity-and-experimentally-induced-sensitisation-in-red-haired-females
#15
Trine Andresen, Dagmar Lunden, Asbjørn M Drewes, Lars Arendt-Nielsen
Introduction and aim Pain sensitivity has been linked to the melanocortin-1 receptor (MC1R) gene. A mutation in MC1R can result in pale skin and red hair in humans and may modulate pain responses in general. Human studies have shown that women with non-functional MC1R's were sensitive to experimental induced cold and heat pain. A study demonstrated that females with red hair required higher dose of anesthesia than females with dark hair to experience analgesia to electrical stimulation. Moreover, women expressing non-functional MC1Rs display greater analgesia from opioid analgesia...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913934/does-co-administration-of-paroxetine-change-oxycodone-analgesia-an-interaction-study-in-chronic-pain-patients
#16
K K Lemberg, T E Heiskanen, M Neuvonen, V K Kontinen, P J Neuvonen, M-L Dahl, E A Kalso
Oxycodone is a strong opioid and it is increasingly used in the management of acute and chronic pain. The pharmacodynamic effects of oxycodone are mainly mediated by the μ-opioid receptor. However, its affinity for the μ-opioid receptor is significantly lower compared with that of morphine and it has been suggested that active metabolites may play a role in oxycodone analgesia. Oxycodone is mainly metabolized by hepatic cytochrome (CYP) enzymes 2D6 and 3A4. Oxycodone is metabolized to oxymorphone, a potent μ-opioid receptor agonist by CYP2D6...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913917/the-mineralocorticoid-receptor-antagonist-spironolactone-enhances-morphine-antinociception
#17
Viljami Jokinen, Tuomas O Lilius, Mikko S Neuvonen, Antti J Väänänen, Mikko O Niemi, Pekka V Rauhala, Eija A Kalso
Aims Spironolactone, an antimineralocorticoid, has been reported to potentiate the cataleptic effect of morphine in the rat. Since no previous research exists on the matter and the interaction might be clinically significant, the effects of spironolactone on morphine antinociception and pharmacokinetics in the rat were investigated. Methods Male SD rats were used to assess the effects of spironolactone on acute morphine-induced antinociception, development of morphine tolerance, and established morphine tolerance in the tail-flick and hot plate tests...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913911/buprenorphine-clinically-useful-but-often-misunderstood
#18
Stephen Butler
Background There are a number of false myths about buprenorphine based on unconfirmed animal data, even from isolated animal organs, and early clinical research. These myths came into textbooks on pharmacology and pain about 30 years ago and have been difficult to eradicate. Animal models of pain and pain relief are notoriously unreliable as predictors of human clinical effects. The fact is that in clinical practice there is NO bell-shaped dose-response curve, there is NO plateau on the dose-response curve, and there is NO antagonist effect from buprenorphine on other mu-opioid agonists...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913894/evaluation-of-a-novel-chemokine-receptor-2-ccr2-antagonist-in-painful-diabetic-polyneuropathy
#19
Jarkko Kalliomäki, Bror Jonzon, Karin Huizar, Michael O'Malley, Anita Andersson, David M Simpson
Background and aims Preclinical data suggest that the chemokine receptor 2 (CCR2) is involved in the pathophysiology of neuropathic pain through modulation of neuronal excitability, synaptic transmission and activation of spinal cord microglia. CCR2-antagonists have shown to be effective in preclinical models of neuropathic pain. The aim of this study was to evaluate the analgesic efficacy, safety and tolerability of a novel CCR2-antagonist, AZD2423, in patients with painful diabetic neuropathy (PDN). Methods This was a double-blind, randomized, parallel-group, multi-center study in patients with symmetric distal sensory polyneuropathy due to type 1 or 2 diabetes and duration of neuropathic pain between 3 months and 5 years...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913859/recovery-after-a-lumbar-disc-herniation-is-dependent-on-a-gender-and-oprm1-asn40asp-genotype-interaction
#20
M B Olsen, L M Jacobsen, E I Schistad, L M Pedersen, L J Rygh, C Røe, J Gjerstad
Background/aims The μ-opioid receptor (OPRM1) is the major target of endogenous opioid peptides and opioid analgesic agents. An important single nucleotide polymorphism (SNP) in this gene is the functional SNP, rs1799971, leading to a substitution of asparagine (Asn) to aspartic acid (Asp) at codon 40 in exon 1. Previous studies have suggested that this SNP may give different phenotypes in males and females. In the present study we therefore investigated whether the OPRM1 Asn40Asp SNP, grouped by gender, could predict clinical outcome regarding progression of pain intensity and disability in patients with discogenic low back pain and sciatica...
December 29, 2017: Scandinavian Journal of Pain
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