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endogenous analgesia

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https://www.readbyqxmd.com/read/28746077/disrupted-offset-analgesia-distinguishes-patients-with-chronic-pain-from-healthy-controls
#1
Hiroyuki Kobinata, Eri Ikeda, Shuo Zhang, Tianjiao Li, Koshi Makita, Jiro Kurata
Offset analgesia (OA) represents a disproportionately large decrease of pain perception after a brief, temporary increment of thermal pain stimulus and was reported attenuated in patients with neuropathic pain. We examined whether OA depends on the increment duration before offset, and whether individual features of OA distinguish patients with chronic pain and healthy controls. We used a Peltier-type thermal stimulator and OA paradigms including 5-, 10-, or 15-s duration of 1°C-increment (T2) over 45°C. We first examined OA response, on the left volar forearm, at 3 different T2's in 40 healthy volunteers, and OA and constant stimulus responses in 12 patients with chronic pain and 12 matched healthy controls...
June 21, 2017: Pain
https://www.readbyqxmd.com/read/28745837/prosecretory-effect-of-loperamide-in-ileal-and-colonic-mucosae-of-mice-displaying-high-or-low-swim-stress-induced-analgesia-associated-with-high-and-low-endogenous-opioid-system-activity
#2
A Wasilewski, A Misicka, M Sacharczuk, J Fichna
BACKGROUND: Irritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and changes in bowel habit. The aim of this study was to characterize the effect of loperamide hydrochloride (LOP) and naloxone hydrochloride (NLX), an opioid agonist and antagonist, respectively, on electrolyte equilibrium in ileal and colonic mucosae and to estimate the possible influence of divergent activity of the endogenous opioid system (EOS) on IBS therapy. METHODS: Two mouse lines bidirectionally selected for high (HA) and low (LA) swim stress-induced analgesia associated with high and low EOS activity were used in this study...
July 26, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28731982/peripheral-oxytocin-receptors-inhibit-the-nociceptive-input-signal-to-spinal-dorsal-horn-wide-dynamic-range-neurons
#3
Abimael González-Hernández, Alfredo Manzano-García, Guadalupe Martínez-Lorenzana, Irma A Tello-García, Martha Carranza, Carlos Arámburo, Miguel Condés-Lara
Oxytocin has emerged as a mediator of endogenous analgesia in behavioral and electrophysiological experiments. In fact, oxytocin receptors (OTRs) in the spinal dorsal horn participate in a selective inhibition of the neuronal activity mediated by Aδ- and C-fibers but not Aβ-fibers. This study shows that OTRs are expressed in the terminal nerve endings and are able to inhibit nociceptive neuronal firing. Indeed, local peripheral oxytocin blocked the first sensorial activity Aδ- and C-fibers recorded in the spinal cord neurons...
July 19, 2017: Pain
https://www.readbyqxmd.com/read/28716934/sigma-1-receptors-control-immune-driven-peripheral-opioid-analgesia-during-inflammation-in-mice
#4
Miguel A Tejada, Angeles Montilla-García, Shane J Cronin, Domagoj Cikes, Cristina Sánchez-Fernández, Rafael González-Cano, M Carmen Ruiz-Cantero, Josef M Penninger, José M Vela, José M Baeyens, Enrique J Cobos
Sigma-1 antagonism potentiates the antinociceptive effects of opioid drugs, so sigma-1 receptors constitute a biological brake to opioid drug-induced analgesia. The pathophysiological role of this process is unknown. We aimed to investigate whether sigma-1 antagonism reduces inflammatory pain through the disinhibition of the endogenous opioidergic system in mice. The selective sigma-1 antagonists BD-1063 and S1RA abolished mechanical and thermal hyperalgesia in mice with carrageenan-induced acute (3 h) inflammation...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28699350/analgesic-properties-of-opioid-nk1-multitarget-ligands-with-distinct-in-vitro-profiles-in-naive-and-chronic-constriction-injury-mice
#5
Joanna Starnowska, Roberto Costante, Karel Guillemyn, Katarzyna Popiolek-Barczyk, Nga N Chung, Carole Lemieux, Attila Keresztes, Joost Van Duppen, Adriano Mollica, John Streicher, Jozef Vanden Broeck, Peter W Schiller, Dirk Tourwé, Joanna Mika, Steven Ballet, Barbara Przewlocka
The lower efficacy of opioids in neuropathic pain may be due to the increased activity of pronociceptive systems such as substance P. We present evidence to support this hypothesis in this work from the spinal cord in a neuropathic pain model in mice. Biochemical analysis confirmed the elevated mRNA and protein level of pronociceptive substance P, the major endogenous ligand of the neurokinin-1 (NK1) receptor, in the lumbar spinal cord of chronic constriction injury (CCI)-mice. To improve opioid efficacy in neuropathic pain, novel compounds containing opioid agonist and neurokinin 1 (NK1) receptor antagonist pharmacophores were designed...
July 26, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28698219/the-transcription-factor-c-ebp%C3%AE-in-the-dorsal-root-ganglion-contributes-to-peripheral-nerve-trauma-induced-nociceptive-hypersensitivity
#6
Zhisong Li, Yuanyuan Mao, Lingli Liang, Shaogen Wu, Jingjing Yuan, Kai Mo, Weihua Cai, Qingxiang Mao, Jing Cao, Alex Bekker, Wei Zhang, Yuan-Xiang Tao
Changes in gene transcription in the dorsal root ganglion (DRG) after nerve trauma contribute to the genesis of neuropathic pain. We report that peripheral nerve trauma caused by chronic constriction injury (CCI) increased the abundance of the transcription factor C/EBPβ (CCAAT/enhancer binding protein β) in the DRG. Blocking this increase mitigated the development and maintenance of CCI-induced mechanical, thermal, and cold pain hypersensitivities without affecting basal responses to acute pain and locomotor activity...
July 11, 2017: Science Signaling
https://www.readbyqxmd.com/read/28671718/antinociceptive-effects-of-low-level-laser-therapy-at-3-and-8%C3%A2-j-cm-2-in-a-rat-model-of-postoperative-pain-possible-role-of-endogenous-opioids
#7
Fabio C Pereira, Julia R Parisi, Caio B Maglioni, Gabriel B Machado, Paulino Barragán-Iglesias, Josie R T Silva, Marcelo L Silva
Low-level laser therapy (LLLT) is the direct application of light to stimulate cell responses (photobiomodulation) to promote tissue healing, reduce inflammation, and induce analgesia; the molecular basis for these effects of LLLT remains unclear. The objective of this study was to evaluate the analgesic effect of LLLT in the rat plantar incision model of postoperative pain as well as to investigate some of the possible mechanisms involved in this effect. Wistar rats were submitted to plantar incision and treated with LLLT (830 nm, continuous-mode, 30 mW/cm(2) , 1-12 J/cm(2) )...
July 3, 2017: Lasers in Surgery and Medicine
https://www.readbyqxmd.com/read/28594147/casein-kinase-1-epsilon-deletion-increases-mu-opioid-receptor-dependent-behaviors-and-binge-eating1
#8
L R Goldberg, S L Kirkpatrick, N Yazdani, K P Luttik, O A Lacki, R Keith Babbs, D F Jenkins, W Evan Johnson, C D Bryant
Genetic and pharmacological studies indicate that casein kinase 1 epsilon (Csnk1e) contributes to psychostimulant, opioid, and ethanol motivated behaviors. We previously used pharmacological inhibition to demonstrate that Csnk1e negatively regulates the locomotor stimulant properties of opioids and psychostimulants. Here, we tested the hypothesis that Csnk1e negatively regulates opioid and psychostimulant reward using genetic inhibition and the conditioned place preference assay in Csnk1e knockout mice. Similar to pharmacological inhibition, Csnk1e knockout mice showed enhanced opioid-induced locomotor activity with the mu opioid receptor agonist fentanyl (0...
June 8, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28574249/synthesis-and-characterization-of-novel-acyl-glycine-inhibitors-of-glyt2
#9
Shannon N Mostyn, Jane E Carland, Susan Shimmon, Renae M Ryan, Tristan Rawling, Robert J Vandenberg
It has been demonstrated previously that the endogenous compound N-arachidonyl-glycine inhibits the glycine transporter GlyT2, stimulates glycinergic neurotransmission, and provides analgesia in animal models of neuropathic and inflammatory pain. However, it is a relatively weak inhibitor with an IC50 of 9 μM and is subject to oxidation via cyclooxygenase, limiting its therapeutic value. In this paper we describe the synthesis and testing of a novel series of monounsaturated C18 and C16 acyl-glycine molecules as inhibitors of the glycine transporter GlyT2...
June 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28530662/pd-l1-inhibits-acute-and-chronic-pain-by-suppressing-nociceptive-neuron-activity-via-pd-1
#10
Gang Chen, Yong Ho Kim, Hui Li, Hao Luo, Da-Lu Liu, Zhi-Jun Zhang, Mark Lay, Wonseok Chang, Yu-Qiu Zhang, Ru-Rong Ji
Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and suppresses immunity through the receptor PD-1 expressed on T cells. However, the role of PD-L1 and PD-1 in regulating pain and neuronal function is unclear. Here we report that both melanoma and normal neural tissues including dorsal root ganglion (DRG) produce PD-L1 that can potently inhibit acute and chronic pain. Intraplantar injection of PD-L1 evoked analgesia in naive mice via PD-1, whereas PD-L1 neutralization or PD-1 blockade induced mechanical allodynia...
July 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28527646/high-dose-amino-acid-administration-achieves-an-anabolic-response-in-type-2-diabetic-patients-that-is-independent-of-glycaemic-control-a-randomized-clinical-trial
#11
Chelsia Gillis, Patricia S Roque, Jürgen Bläss, Albert Urwyler, Harald Schepperle, Guido Kunz, Thomas Peters, Thomas Schricker, Linda Wykes, Andrea Kopp Lugli
BACKGROUND & AIMS: Surgical stress provokes protein catabolism and hyperglycaemia that is enhanced in patients with type 2 diabetes (T2DM), and increases perioperative morbidity. This study hypothesized that perioperative administration of high dose intravenous (IV) amino acids (AA) will augment protein balance in T2DM patients receiving tight plasma glucose control via continuous IV insulin compared to standard plasma glucose control via subcutaneous (SC) insulin sliding scale. METHODS: Eighteen patients with well-controlled T2DM (HbA1C% < 7...
May 3, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28476692/oxytocin-administration-during-spontaneous-labor-guidelines-for-clinical-practice-chapter-7-epidural-analgesia-and-use-of-oxytocin-during-spontaneous-labor
#12
C Fischer
No abstract text is available yet for this article.
May 2, 2017: Journal of gynecology obstetrics and human reproduction
https://www.readbyqxmd.com/read/28424989/t-lymphocyte-derived-enkephalins-reduce-th1-th17-colitis-and-associated-pain-in-mice
#13
Lilian Basso, Laure Garnier, Arnaud Bessac, Jérôme Boué, Catherine Blanpied, Nicolas Cenac, Sophie Laffont, Gilles Dietrich
BACKGROUND: Endogenous opioids, including enkephalins, are fundamental regulators of pain. In inflammatory conditions, the local release of opioids by leukocytes at the inflammatory site inhibits nociceptor firing, thereby inducing analgesia. Accordingly, in chronic intestinal Th1/Th17-associated inflammation, enkephalins released by colitogenic CD4(+) T lymphocytes relieve inflammation-induced visceral pain. The present study aims to investigate whether mucosal T-cell-derived enkephalins also exhibit a potent anti-inflammatory activity as described for exogenous opioid drugs in Th1/Th17-associated colitis...
April 19, 2017: Journal of Gastroenterology
https://www.readbyqxmd.com/read/28404687/selective-calcium-dependent-inhibition-of-atp-gated-p2x3-receptors-by-bisphosphonate-induced-endogenous-atp-analog-apppi
#14
Yevheniia Ishchenko, Anastasia Shakirzyanova, Raisa Giniatullina, Andrei Skorinkin, Genevieve Bart, Petri Turhanen, Jorma A Määttä, Jukka Mönkkönen, Rashid Giniatullin
Pain is the most unbearable symptom accompanying primary bone cancers and bone metastases. Bone resorptive disorders are often associated with hypercalcemia, contributing to the pathologic process. Nitrogen-containing bisphosphonates (NBPs) are efficiently used to treat bone cancers and metastases. Apart from their toxic effect on cancer cells, NBPs also provide analgesia via poorly understood mechanisms. We previously showed that NBPs, by inhibiting the mevalonate pathway, induced formation of novel ATP analogs such as ApppI [1-adenosin-5'-yl ester 3-(3-methylbut-3-enyl) triphosphoric acid diester], which can potentially be involved in NBP analgesia...
June 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28395733/optical-control-of-pain-in-vivo-with-a-photoactive-mglu5-receptor-negative-allosteric-modulator
#15
Joan Font, Marc López-Cano, Serena Notartomaso, Pamela Scarselli, Paola Di Pietro, Roger Bresolí-Obach, Giuseppe Battaglia, Fanny Malhaire, Xavier Rovira, Juanlo Catena, Jesús Giraldo, Jean-Philippe Pin, Víctor Fernández-Dueñas, Cyril Goudet, Santi Nonell, Ferdinando Nicoletti, Amadeu Llebaria, Francisco Ciruela
Light-operated drugs constitute a major target in drug discovery, since they may provide spatiotemporal resolution for the treatment of complex diseases (i.e. chronic pain). JF-NP-26 is an inactive photocaged derivative of the metabotropic glutamate type 5 (mGlu5) receptor negative allosteric modulator raseglurant. Violet light illumination of JF-NP-26 induces a photochemical reaction prompting the active-drug's release, which effectively controls mGlu5 receptor activity both in ectopic expressing systems and in striatal primary neurons...
April 11, 2017: ELife
https://www.readbyqxmd.com/read/28393429/lack-of-analgesic-synergy-of-the-cholecystokinin-receptor-antagonist-proglumide-and-spinal-cord-stimulation-for-the-treatment-of-neuropathic-pain-in-rats
#16
Shinsuke Inoue, Lisa M Johanek, Kathleen A Sluka
OBJECTIVE: Neuropathic pain is difficult to manage and treat. Spinal cord stimulation (SCS) has become an established procedure for treating chronic neuropathic pain that is refractory to pharmacological therapy. In order to achieve better analgesia, a number of studies have evaluated the effectiveness of combining drug therapy with SCS. Cholecystokinin antagonists, such as proglumide, enhance the analgesic efficacy of endogenous opioids in animal models of pain. We previously reported that both systemic and spinal administration of proglumide enhances analgesia produced by both low- and high-frequency transcutaneous electrical nerve stimulation (TENS)...
April 10, 2017: Neuromodulation: Journal of the International Neuromodulation Society
https://www.readbyqxmd.com/read/28387464/a-novel-ph-controlled-hydrogen-sulfide-donor-protects-gastric-mucosa-from-aspirin-induced-injury
#17
Chun-Tao Yang, Zhen-Zhen Lai, Ze-Hang Zheng, Jian-Ming Kang, Ming Xian, Rui-Yu Wang, Kun Shi, Fu-Hui Meng, Xiang Li, Li Chen, Hui Zhang
Hydrogen sulphide (H2 S) serves as a vital gastric mucosal defence under acid condition. Non-steroidal anti-inflammatory drugs (NSAIDs) are among widely prescribed medications with effects of antipyresis, analgesia and anti-inflammation. However, their inappropriate use causes gastric lesions and endogenous H2 S deficiency. In this work, we reported the roles of a novel pH-controlled H2 S donor (JK-1) in NSAID-related gastric lesions. We found that JK-1 could release H2 S under mild acidic pH and increase solution pH value...
April 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28365372/endogenous-opioid-function-and-responses-to-morphine-the-moderating-effects-of-anger-expressiveness
#18
John W Burns, Stephen Bruehl, Christopher R France, Erik Schuster, Daria Orlowska, Melissa Chont, Rajnish K Gupta, Asokumar Buvanendran
Long-term use of opioid analgesics may be ineffective or associated with significant negative side effects for some people. At present, there is no sound method of identifying optimal opioid candidates. Individuals with chronic low back pain (n = 89) and healthy control individuals (n = 102) underwent ischemic pain induction with placebo, opioid blockade (naloxone), and morphine in counterbalanced order. They completed the Spielberger Anger-Out subscale. Endogenous opioid function × Anger-out × Pain status (chronic pain, healthy control) interactions were tested for morphine responses to ischemic threshold, tolerance, and pain intensity (McGill Sensory and Affective subscales) and side effects...
March 30, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28363796/structure-constrained-endomorphin-analogs-display-differential-antinociceptive-mechanisms-in-mice-after-spinal-administration
#19
Yuan Wang, Jingjing Zhou, Xin Liu, Long Zhao, Zhaojuan Wang, Xianghui Zhang, Kezhou Wang, Linqing Wang, Rui Wang
We previously reported a series of novel endomorphin analogs with unnatural amino acid modifications. These analogs display good binding affinity and functional activity toward the μ opioid receptor (MOP). In the present study, we further investigated the spinal antinociceptive activity of these compounds. The analogs were potent in several nociceptive models. Opioid antagonists and antibodies against several endogenous opioid peptides were used to determine the mechanisms of action of these peptides. Intrathecal pretreatment with naloxone and β-funaltrexamine (β-FNA) effectively inhibited analog-induced analgesia, demonstrating that activity of the analogs is regulated primarily through MOP...
May 2017: Peptides
https://www.readbyqxmd.com/read/28360106/ca-2-and-calpain-mediate-capsaicin-induced-ablation-of-axonal-terminals-expressing-transient-receptor-potential-vanilloid-1
#20
Sheng Wang, Sen Wang, Jamila Asgar, John Joseph, Jin Y Ro, Feng Wei, James N Campbell, Man-Kyo Chung
Capsaicin is an ingredient in spicy peppers that produces burning pain by activating transient receptor potential vanilloid 1 (TRPV1), a Ca(2+)-permeable ion channel in nociceptors. Capsaicin has also been used as an analgesic, and its topical administration is approved for the treatment of certain pain conditions. The mechanisms underlying capsaicin-induced analgesia likely involve reversible ablation of nociceptor terminals. However, the mechanisms underlying these effects are not well understood. To visualize TRPV1-lineage axons, a genetically engineered mouse model was used in which a fluorophore is expressed under the TRPV1 promoter...
May 19, 2017: Journal of Biological Chemistry
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