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https://www.readbyqxmd.com/read/29155208/inflammatory-renin-angiotensin-system-disruption-attenuates-sensory-hyperinnervation-and-mechanical-hypersensitivity-in-a-rat-model-of-provoked-vestibulodynia
#1
Anuradha Chakrabarty, Zhaohui Liao, Ying Mu, Peter G Smith
Vestibulodynia is characterized by peri-vaginal mechanical hypersensitivity, hyperinnervation, and abundant inflammatory cells expressing renin-angiotensin system proteins. We developed a tractable rat model of vestibulodynia to further assess the contributions of the renin-angiotensin system. Complete Freund's adjuvant (CFA) injected into the posterior vestibule induced marked vestibular hypersensitivity throughout a 7-day test period. Numbers of axons immunoreactive for PGP9.5, calcitonin gene-related peptide, and GFRα2 were increased...
November 15, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/29150865/enhanced-mu-opioid-receptor-dependent-opioidergic-modulation-of-striatal-cholinergic-transmission-in-dyt1-dystonia
#2
Giulia Ponterio, Annalisa Tassone, Giuseppe Sciamanna, Valentina Vanni, Maria Meringolo, Massimo Santoro, Nicola Biagio Mercuri, Paola Bonsi, Antonio Pisani
BACKGROUND: Mu opioid receptor activation modulates acetylcholine release in the dorsal striatum, an area deeply involved in motor function, habit formation, and reinforcement learning as well as in the pathophysiology of different movement disorders, such as dystonia. Although the role of opioids in drug reward and addiction is well established, their involvement in motor dysfunction remains largely unexplored. METHODS: We used a multidisciplinary approach to investigate the responses to mu activation in 2 mouse models of DYT1 dystonia (Tor1a(+/Δgag) mice, Tor1a(+/-) torsinA null mice, and their respective wild-types)...
November 18, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29148033/4218t-c-polymorphism-associations-with-post-cesarean-patient-controlled-epidural-fentanyl-consumption-and-pain-perception
#3
W Xie, W Zhuang, L Chen, W Xie, C Jiang, N Liu
BACKGROUND: The utilization of intrathecal opioids is an efficacious component of post-cesarean section pain management. Given that growing evidence indicates that calcitonin gene-related peptide (CGRP) plays a key role in the development of peripheral sensitization and is associated with enhanced pain, we hypothesized that CGRP 4218T/C polymorphism is associated with the variability in fentanyl consumption for post-cesarean analgesia. METHODS: We recruited 548 patients who presented for elective cesarean delivery, and used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to analyze CGRP 4218T/C polymorphism...
November 17, 2017: Acta Anaesthesiologica Scandinavica
https://www.readbyqxmd.com/read/29129606/transgenerational-blunting-of-morphine-induced-corticosterone-secretion-is-associated-with-dysregulated-gene-expression-in-male-offspring
#4
Fair M Vassoler, Anika M Toorie, Elizabeth M Byrnes
A number of parental experiences, even when occurring prior to conception, have been shown to induce transgenerational effects beyond the first generation. In the case of exposure to drugs of abuse, studies in rodents suggest that offspring demonstrate significant differences in how they respond to the drug to which their parent was exposed. We have previously observed significant alterations in morphine analgesia, conditioned place preference and self-administration in the offspring of females exposed to morphine during adolescent development...
November 9, 2017: Brain Research
https://www.readbyqxmd.com/read/29127441/verification-of-a-genetic-locus-for-methamphetamine-intake-and-the-impact-of-morphine
#5
Emily C Eastwood, Amy J Eshleman, Aaron Janowsky, Tamara J Phillips
A quantitative trait locus (QTL) on proximal chromosome (Chr) 10 accounts for > 50% of the genetic variance in methamphetamine (MA) intake in mice selectively bred for high (MAHDR) and low (MALDR) voluntary MA drinking. The µ-opioid receptor (MOP-r) gene, Oprm1, resides at the proximal end of Chr 10, and buprenorphine reduces MA intake in MAHDR mice. However, this drug has only partial agonist effects at MOP-r. We investigated the impact of a full MOP-r agonist, morphine, on MA intake and saccharin intake, measured MOP-r density and affinity in several brain regions of the MA drinking lines and their C57BL/6J (B6) and DBA/2J (D2) progenitor strains, and measured MA intake in two congenic strains of mice to verify the QTL and reduce the QTL interval...
November 10, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/29124744/usefulness-of-knockout-mice-to-clarify-the-role-of-the-opioid-system-in-chronic-pain
#6
REVIEW
Rafael Maldonado, Josep Eladi Baños, David Cabañero
Several lines of knockout mice deficient in the genes encoding each component of the endogenous opioid system have been used for decades to clarify the specific role of the different opioid receptors and peptide precursors in multiple physiopathological conditions. The use of these genetically modified mice has improved our knowledge of the specific involvement of each endogenous opioid component in nociceptive transmission during acute and chronic pain conditions. The present review summarizes the recent advances obtained using these genetic tools in understanding the role of the opioid system in the pathophysiological mechanisms underlying chronic pain...
November 10, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29098668/similarities-and-differences-in-genetics
#7
Yang Zhang, Yan Sun, Jie Liang, Lin Lu, Jie Shi
Similar symptomatology manifestations and high co-morbidity in substance and non-substance addictions suggest that there may be a common pathogenesis between them. Associated with impulse control and emotional processing, the monoamine neurotransmitter system genes are suggested to be related to both substance and non-substance addictions, such as dopamine (DA) system, 5-hydroxytryptamine/serotonin (5-HT) system, the endogenous opioid system and so on. Here we reviewed the similarities and differences in genetics between classic substance addiction and common types of non-substance addiction, e...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29094432/mu-opioid-receptors-in-gabaergic-neurons-of-the-forebrain-promote-alcohol-reward-and-drinking
#8
Sami Ben Hamida, Laura-Joy Boulos, Michael McNicholas, Pauline Charbogne, Brigitte Lina Kieffer
Mu opioid receptors (MORs) are widely distributed throughout brain reward circuits and their role in drug and social reward is well established. Substantial evidence has implicated MOR and the endogenous opioid system in alcohol reward, but circuit mechanisms of MOR-mediated alcohol reward and intake behavior remain elusive, and have not been investigated by genetic approaches. We recently created conditional knockout (KO) mice targeting the Oprm1 gene in GABAergic forebrain neurons. These mice (Dlx-MOR KO) show a major MOR deletion in the striatum, whereas receptors in midbrain (including the Ventral Tegmental Area or VTA) and hindbrain are intact...
November 2, 2017: Addiction Biology
https://www.readbyqxmd.com/read/29079719/integrated-proteomic-and-transcriptomic-analysis-revealslong-noncoding-rna-hotair-promotes-hepatocellular-carcinoma-cell-proliferation-by-regulating-opioid-growth-factor-receptor-ogfr
#9
Ying Wu, Qian Xiong, Siting Li, Xue Yang, Feng Ge
Long non-coding RNA HOX transcript antisense RNA (HOTAIR) is involved in human tumorigenesis and is dysregulated in hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying HOTAIR functions in HCC are largely unknown. Here, we employed an integrated transcriptomic and quantitative proteomic analysis to systematically explore the regulatory role of HOTAIR in HCC. A total of 673 transcripts and 293 proteins were found to be dysregulated after HOTAIR inhibition. Bioinformatics studies indicated that differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) are involved in many biological processes, especially cancer-related signaling pathways...
October 27, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29075135/dnmt3a-methylation-in-neuropathic-pain
#10
Cuijie Shao, Yong Gao, Dan Jin, Xin Xu, Shuying Tan, Hui Yu, Qingxiang Zhao, Li Zhao, Wansheng Wang, Deqiang Wang
BACKGROUND: Mu opioid receptor (MOR) plays a crucial role in mediating analgesic effects of opioids and is closely associated with the pathologies of neuropathic pain. Previous studies have reported that peripheral nerve injury downregulates MOR expression, but the epigenetic mechanisms remain unknown. OBJECTIVE: Therefore, we investigated DNA methyltransferase3a (DNMT3a) expression or methylation changes within MOR promoter in the spinal cord in a neuropathic pain induced by a chronic constriction injury (CCI) mouse model and further determined whether these injury-associated changes are reversible by pharmacological interventions...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/29055075/association-between-genetic-polymorphisms-and-pain-sensitivity-in-patients-with-hip-osteoarthritis
#11
Anne E Olesen, Lecia M Nielsen, Søren Feddersen, Joachim Erlenwein, Frank Petzke, Michael Przemeck, Lona L Christrup, Asbjørn M Drewes
BACKGROUND: Factors such as age, gender and genetic polymorphisms may explain individual difference in pain phenotype. Genetic associations to pain sensitivity have previously been investigated in osteoarthritis patients with focus on the P2X7, TRPV1 and TACR1 genes. However, other genes may play a role as well. Osteoarthritis is a common joint disease and many patients suffering from this disease are thought to have increased sensitivity to noxious stimuli resulting from sensitization in the nociceptive system...
October 20, 2017: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/29054455/dadle-enhances-viability-and-anti-inflammatory-effect-of-human-mscs-subjected-to-serum-free-apoptotic-condition-in-part-via-the-dor-pi3k-akt-pathway
#12
L Vinod Kumar Reddy, Dwaipayan Sen
AIM: Nutritional deprivation and inflammation-rich zones are the major causative reasons for poor survivability of transplanted mesenchymal stem cells (MSCs). Therefore in the present study, we demonstrated the cytoprotective and anti-inflammatory effects of activated delta (δ)-opioid receptor (DOR) with synthetic peptide [D-Ala(2), D-Leu(5)]-enkephalin (DADLE) treatment on human MSCs cultured in serum-starved condition. MAIN METHODS: Cell viability was measured using MTT and Annexin V/PI assays...
October 19, 2017: Life Sciences
https://www.readbyqxmd.com/read/29054049/individual-variability-in-clinical-effect-and-tolerability-of-opioid-analgesics-importance-of-drug-interactions-and-pharmacogenetics
#13
REVIEW
Vigdis Solhaug, Espen Molden
BACKGROUND: As pain is often a comorbid condition, many patients use opioid analgesics in combination with several other drugs. This implies a generally increased risk of drug interactions, which along with inherent pharmacogenetic variability and other factors may cause differences in therapeutic response of opioids. AIM: To provide an overview of interactions and pharmacogenetic variability of relevance for individual differences in effect and tolerability of opioid analgesics, which physicians and other healthcare professionals should be aware of in clinical practice...
October 17, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29039297/the-impact-of-periconceptional-alcohol-exposure-on-fat-preference-and-gene-expression-in-the-mesolimbic-reward-pathway-in-adult-rat-offspring
#14
E S Dorey, C L Cullen, D Lucia, K M Mah, M-L Roy Manchadi, B S Muhlhausler, K M Moritz
Alcohol consumption around the time of conception is highly prevalent in Western countries. Exposure to ethanol levels during gestation has been associated with altered development of the mesolimbic reward pathway in rats and increased propensity to addiction, however the effect of exposure only around the time of conception is unknown. The current study investigated the effects of periconceptional alcohol exposure (PC:EtOH) on alcohol and palatable food preferences and gene expression in the ventral tegmental area (VTA) and the nucleus accumbens of the adult offspring...
October 17, 2017: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/29020387/reversal-of-stress-induced-social-interaction-deficits-by-buprenorphine
#15
Caroline A Browne, Edgardo Falcon, Shivon A Robinson, Olivier Berton, Irwin Lucki
Background: Patients with post-traumatic stress disorder (PTSD) frequently report persistent problems with social interactions, emerging after a traumatic experience. Chronic social defeat stress (CSDS) is a widely used rodent model of stress that produces robust and sustained social avoidance behavior. The avoidance of other rodents can be reversed by 28 days of treatment with selective serotonin reuptake inhibitors (SSRIs), the only pharmaceutical class approved by the U. S. Food and Drug Administration for treating PTSD...
August 31, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29016850/mice-lacking-cyclin-dependent-kinase-like-5-manifest-autistic-and-adhd-like-behaviors
#16
Cian-Ling Jhang, Tzyy-Nan Huang, Yi-Ping Hsueh, Wenlin Liao
Neurodevelopmental disorders frequently share common clinical features and appear high rate of comorbidity, such as those present in patients with attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD). While characterizing behavioral phenotypes in the mouse model of cyclin-dependent kinase-like 5 (CDKL5) disorder, a neurodevelopmental disorder caused by mutations in the X-linked gene encoding CDKL5, we found that these mice manifested behavioral phenotypes mimicking multiple key features of ASD, such as impaired social interaction and communication, as well as increased stereotypic digging behaviors...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28992386/interaction-between-the-%C3%AE-opioid-receptor-gene-and-the-number-of-heavy-drinking-peers-on-alcohol-use
#17
Michelle J Zaso, Stephen A Maisto, Stephen J Glatt, John M Belote, Aesoon Park
BACKGROUND: The presence of heavy-drinking peers may trigger genetic vulnerabilities to alcohol use. Limited correlational findings, albeit mixed as a function of age, suggest that carriers of a μ-opioid receptor (OPRM1) G allele may be more vulnerable than noncarriers to alcohol-promoting perceived peer environments. However, research has not yet examined such genetic susceptibility to actual (rather than perceived) peer environments through an experimental, ad libitum alcohol administration design...
October 9, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28991183/orexin-receptor-multimerization-versus-functional-interactions-neuropharmacological-implications-for-opioid-and-cannabinoid-signalling-and-pharmacogenetics
#18
Miles D Thompson, Takeshi Sakurai, Innocenzo Rainero, Mary C Maj, Jyrki P Kukkonen
Orexins/hypocretins are neuropeptides formed by proteolytic cleavage of a precursor peptide, which are produced by neurons found in the lateral hypothalamus. The G protein-coupled receptors (GPCRs) for these ligands, the OX₁ and OX₂ orexin receptors, are more widely expressed throughout the central nervous system. The orexin/hypocretin system has been implicated in many pathways, and its dysregulation is under investigation in a number of diseases. Disorders in which orexinergic mechanisms are being investigated include narcolepsy, idiopathic sleep disorders, cluster headache and migraine...
October 8, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28991118/truncated-%C3%AE-opioid-receptors-with-6-transmembrane-domains-are-essential-for-opioid-analgesia
#19
Zhigang Lu, Jin Xu, Mingming Xu, Grace C Rossi, Susruta Majumdar, Gavril W Pasternak, Ying-Xian Pan
BACKGROUND: Most clinical opioids act through μ-opioid receptors. They effectively relieve pain but are limited by side effects, such as constipation, respiratory depression, dependence, and addiction. Many efforts have been made toward developing potent analgesics that lack side effects. Three-iodobenzoyl-6β-naltrexamide (IBNtxA) is a novel class of opioid active against thermal, inflammatory, and neuropathic pain, without respiratory depression, physical dependence, and reward behavior...
October 4, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28985716/selection-of-opioids-for-cancer-related-pain-using-a-biomarker-a-randomized-multi-institutional-open-label-trial-relief-study
#20
Hiromichi Matsuoka, Junji Tsurutani, Yasutaka Chiba, Yoshihiko Fujita, Masato Terashima, Takeshi Yoshida, Kiyohiro Sakai, Yoichi Otake, Atsuko Koyama, Kazuto Nishio, Kazuhiko Nakagawa
BACKGROUND: Cancer patients experience pain that has physiological, sensory, affective, cognitive, behavioral, and sociocultural dimensions. Opioids are used in treatment of pain in patients with various types of cancer. We previously showed that the catechol-O-methyltransferase (COMT) genotype is related to the plasma level of morphine and the required dose of morphine in an exploratory prospective study. The findings showed that a group of patients with a GG single nucleotide polymorphism (SNP) rs4680 in COMT required a significantly higher dose of morphine than a non-GG group...
October 6, 2017: BMC Cancer
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