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https://www.readbyqxmd.com/read/27898491/psychosocial-factors-predict-opioid-analgesia-via-endogenous-opioid-function
#1
John W Burns, Stephen Bruehl, Christopher R France, Erik Schuster, Daria Orlowska, Asokumar Buvanendran, Melissa Chont, Rajnish K Gupta
Use of opioid analgesics for management of chronic nonmalignant pain has become common, yet there are presently no well-validated predictors of optimal opioid analgesic efficacy. We examined whether psychosocial factors (e.g. depressive symptoms) predicted changes in spontaneous low back pain following administration of opioid analgesics, and whether endogenous opioid (EO) function mediated these relationships. Participants with chronic low back pain but who were not chronic opioid users (N = 89) underwent assessment of low back pain intensity pre- and post-drug in three (counterbalanced) conditions: 1) placebo, 2) intravenous naloxone, 3) intravenous morphine...
November 18, 2016: Pain
https://www.readbyqxmd.com/read/27798132/gi-dreadd-expression-in-peripheral-nerves-produces-ligand-dependent-analgesia-as-well-as-ligand-independent-functional-changes-in-sensory-neurons
#2
Jami L Saloman, Nicole N Scheff, Lindsey M Snyder, Sarah E Ross, Brian M Davis, Michael S Gold
: Designer receptors exclusively activated by designer drugs (DREADDs) are an advanced experimental tool that could potentially provide a novel approach to pain management. In particular, expression of an inhibitory (Gi-coupled) DREADD in nociceptors might enable ligand-dependent analgesia. To test this possibility, TRPV1-cre mice were used to restrict expression of Gi-DREADDs to predominantly C-fibers. Whereas baseline heat thresholds in both male and female mice expressing Gi-DREADD were normal, 1 mg/kg clozapine-N-oxide (CNO) produced a significant 3 h increase in heat threshold that returned to baseline by 5 h after injection...
October 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27774136/combined-interactions-with-i1-i2-imidazoline-binding-sites-and-%C3%AE-2-adrenoceptors-to-manage-opioid-addiction
#3
Maria Elena Giusepponi, Carlo Cifani, Maria Vittoria Micioni Di Bonaventura, Laura Mattioli, Alan Hudson, Eleonora Diamanti, Fabio Del Bello, Mario Giannella, Valerio Mammoli, Corinne Dalila Paoletti, Alessandro Piergentili, Maria Pigini, Wilma Quaglia
Tolerance and dependence associated with chronic opioid exposure result from molecular, cellular, and neural network adaptations. Such adaptations concern opioid and nonopioid systems, including α2-adrenoceptors (α2-ARs) and I1- and I2-imidazoline binding sites (IBS). Agmatine, one of the hypothesized endogenous ligands of IBS, targeting several systems including α2-ARs and IBS, proved to be able to regulate opioid-induced analgesia and to attenuate the development of tolerance and dependence. Interested in the complex pharmacological profile of agmatine and considering the nature of its targets, we evaluated two series of imidazolines, rationally designed to simultaneously interact with I1-/I2-IBS or I1-/I2-IBS/α2-ARs...
October 13, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27748566/mu-and-delta-opioid-receptor-knockout-mice-show-increased-colonic-sensitivity
#4
D Reiss, R A Ceredig, T Secher, J Boué, F Barreau, G Dietrich, C Gavériaux-Ruff
BACKGROUND: Opiates act through opioid receptors to diminish pain. Here, we investigated whether mu (MOR) and delta (DOR) receptor endogenous activity assessed in the whole mouse body or in particular at peripheral receptors on primary nociceptive neurons, control colonic pain. METHODS: We compared global MOR and DOR receptor knockout (KO) mice, mice with a conditional deletion of MOR and DOR in Nav1.8-positive nociceptive primary afferent neurons (cKO), and control floxed mice of both genders for visceral sensitivity...
October 17, 2016: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/27703511/effect-of-systemic-injection-of-heterogenous-and-homogenous-opioids-on-peripheral-cellular-immune-response-in-rats-with-bone-cancer-pain-a-comparative-study
#5
Jun-Ying Du, Yi Liang, Jun-Fan Fang, Yong-Liang Jiang, Xiao-Mei Shao, Xiao-Fen He, Jian-Qiao Fang
Exogenous and endogenous opioids have been shown to modulate the immune system. Morphine-induced immunosuppression has been investigated extensively. However, the immune-regulating function of endogenous opioid peptides is unclear. The present study aimed to evaluate the difference in effects on cellular immune function between recombinant rat β-endorphin (β-EP; 50 µg/kg) and plant source morphine (10 mg/kg) via intraperitoneal injection treatment in a rat model of bone cancer pain. Walker 256 cells were injected into a tibial cavity injection to establish the bone cancer pain model...
October 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27663259/increasing-spinal-5-ht2a-receptor-responsiveness-mediates-anti-allodynic-effect-and-potentiates-fluoxetine-efficacy-in-neuropathic-rats-evidence-for-gaba-release
#6
Amandine Dupuis, Anne-Sophie Wattiez, Jérémy Pinguet, Damien Richard, Frédéric Libert, Maryse Chalus, Youssef Aissouni, Benoit Sion, Denis Ardid, Philippe Marin, Alain Eschalier, Christine Courteix
Antidepressants are one of the first line treatments for neuropathic pain but their use is limited by the incidence and severity of side effects of tricyclics and the weak effectiveness of selective serotonin reuptake inhibitors (SSRIs). Serotonin type 2A (5-HT2A) receptors interact with PDZ proteins that regulate their functionality and SSRI efficacy to alleviate pain. We investigated whether an interfering peptide (TAT-2ASCV) disrupting the interaction between 5-HT2A receptors and associated PDZ proteins would improve the treatment of traumatic neuropathic allodynia...
September 20, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27634619/trpm8-and-migraine
#7
Greg Dussor, Yu-Qing Cao
Migraine is among the most common diseases on earth and one of the most disabling, the latter due in large part to poor treatment efficacy. Development of new therapeutics is dependent on the identification of mechanisms contributing to migraine and discovery of targets for new drugs. Numerous genome-wide association studies (GWAS) have implicated the transient receptor-potential M8 (TRPM8) channel in migraine. This channel is predominantly expressed on peripheral sensory neurons and is known as the sensor for cold temperature in cutaneous tissue but is also expressed on deep visceral afferents where cold is not likely a stimulus...
October 2016: Headache
https://www.readbyqxmd.com/read/27616608/preserved-capacity-for-placebo-analgesia-in-the-elderly
#8
Nathalie Wrobel, Tahmine Fadai, Stefanie Brassen, Ulrike Bingel
: The prevalence of chronic pain rises with increasing age. It has been suggested that the mechanisms responsible for the development of chronic pain overlap with mechanisms involved in aging, potentially implicating age-related changes in descending modulatory pathways. This observation raises the question whether other forms of endogenous pain modulation, in particular placebo analgesia, become compromised with age. Because of the known contribution of placebo effects to analgesic treatment outcomes this question is of important clinical relevance...
September 13, 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/27605249/distinct-roles-of-exogenous-opioid-agonists-and-endogenous-opioid-peptides-in-the-peripheral-control-of-neuropathy-triggered-heat-pain
#9
Dominika Labuz, Melih Ö Celik, Andreas Zimmer, Halina Machelska
Neuropathic pain often results from peripheral nerve damage, which can involve immune response. Local leukocyte-derived opioid peptides or exogenous opioid agonists inhibit neuropathy-induced mechanical hypersensitivity in animal models. Since neuropathic pain can also be augmented by heat, in this study we investigated the role of opioids in the modulation of neuropathy-evoked heat hypersensitivity. We used a chronic constriction injury of the sciatic nerve in wild-type and opioid peptide-knockout mice, and tested opioid effects in heat and mechanical hypersensitivity using Hargreaves and von Frey tests, respectively...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27571257/str-324-a-stable-analog-of-opiorphin-causes-analgesia-in-postoperative-pain-by-activating-endogenous-opioid-receptor-dependent-pathways
#10
Philippe Sitbon, Alain Van Elstraete, Leila Hamdi, Victor Juarez-Perez, Jean-Xavier Mazoit, Dan Benhamou, Catherine Rougeot
BACKGROUND: Opiorphin is a naturally occurring potent analgesic human peptide. It protects enkephalins from degradation and inhibits pain perception in various acute pain models via activation of endogenous opioid pathways. However, the efficacy of opiorphin continuous infusion and its chemically stable form, STR-324, in postoperative pain is unknown. METHODS: Using the Brennan model of plantar incision-induced hypersensitivity, the authors examined the postsurgical analgesic response to mechanical and thermal stimuli of 7-day continuously intravenously infused drugs (8 to 10 rats per group)...
November 2016: Anesthesiology
https://www.readbyqxmd.com/read/27532001/neuroimmune-interaction-in-the-regulation-of-peripheral-opioid-mediated-analgesia-in-inflammation
#11
REVIEW
Susan Hua
Peripheral immune cell-mediated analgesia in inflammation is an important endogenous mechanism of pain control. Opioid receptors localized on peripheral sensory nerve terminals are activated by endogenous opioid peptides released from immune cells to produce significant analgesia. Following transendothelial migration of opioid-containing leukocytes into peripheral sites of inflammation, opioid peptides are released into a harsh milieu associated with an increase in temperature, low pH, and high proteolytic activity...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27523794/heterodimerization-of-the-kappa-opioid-receptor-and-neurotensin-receptor-1-contributes-to-a-novel-%C3%AE-arrestin-2-biased-pathway
#12
Haiqing Liu, Yanjun Tian, Bingyuan Ji, Hai Lu, Qing Xin, Yunlu Jiang, Liangcai Ding, Jingmei Zhang, Jing Chen, Bo Bai
Together with its endogenous ligands (dynorphin), the kappa opioid receptor (KOR) plays an important role in modulating various physiological and pharmacological responses, with a classical G protein-coupled pathway mediating analgesia and non-G protein-dependent pathway, especially the β-arrestin-dependent pathway, eliciting side effects of dysphoria, aversion, drug-seeking in addicts, or even relapse to addiction. Although mounting evidence has verified a functional overlap between dynorphin/KOR and neurotensin/neurotensin receptor 1 (NTSR1) systems, little is known about direct interaction between the two receptors...
November 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27503688/%C3%A2%C2%B51-opioid-receptors-in-the-dorsomedial-and-ventrolateral-columns-of-the-periaqueductal-grey-matter-are-critical-for-the-enhancement-of-post-ictal-antinociception
#13
Renato Leonardo de Freitas, Priscila Medeiros, Asmat Ullah Khan, Norberto Cysne Coimbra
Generalised tonic and tonic-clonic seizures are followed by significant increase in nociceptive thresholds in both laboratory animals and humans. The endogenous opioid peptides play a role in antinociceptive signalling, and the periaqueductal grey matter (PAG) is recruited to induce analgesia. Thus, the aim of this investigation was to evaluate the role of µ1 -opioid receptors in the dorsomedial (dm) and ventrolateral (vl) columns of PAG in post-ictal antinociception. Pentylenetetrazole (PTZ; 64 mg/kg), which is an ionotropic GABA-mediated Cl(-) influx antagonist, was intraperitoneally (IP) administered to induce tonic-clonic seizures in Wistar rats...
December 2016: Synapse
https://www.readbyqxmd.com/read/27461371/endocannabinoids-control-vesicle-release-mode-at-midbrain-periaqueductal-grey-inhibitory-synapses
#14
Karin R Aubrey, Geoffrey M Drew, Hyo-Jin Jeong, Benjamin K Lau, Christopher W Vaughan
The midbrain periaqueductal grey (PAG) has a crucial role in coordinating endogenous analgesic responses to physiological and psychological stressors. Endocannabinoids are thought to mediate a form of stress-induced analgesia within the PAG by relieving GABAergic inhibition of output neurons, a process known as disinhibition. This disinhibition is thought to be achieved by a presynaptic reduction in GABA release probability. We examined whether other mechanisms have a role in endocannabinoid modulation of GABAergic synaptic transmission within the rat PAG...
July 27, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27454261/an-overview-of-offset-analgesia-and-the-comparison-with-conditioned-pain-modulation-a-systematic-literature-review
#15
Linda Hermans, Patrick Calders, Jessica Van Oosterwijck, Ellen Verschelde, Eva Bertel, Mira Meeus
BACKGROUND: Offset analgesia (OA) is an increasingly described phenomenon to measure endogenous pain inhibition, in which a greater decrease in pain intensity is experienced than would be predicted by the decrease in painful stimulation. The temporal filtering in this OA phenomenon differs from the spatial filtering in the commonly described conditioned pain modulation (CPM). Yet, the knowledge on the efficacy of OA in chronic pain patients is scarce, compared to CPM efficacy. OBJECTIVE: This systematic review has been conducted to provide an overview of the current knowledge regarding OA, and to compare it to CPM...
July 2016: Pain Physician
https://www.readbyqxmd.com/read/27370939/electroacupuncture-analgesia-with-different-frequencies-is-mediated-via-different-opioid-pathways-in-acute-visceral-hyperalgesia-rats
#16
Debo Qi, Shuqin Wu, Yuhua Zhang, Weimin Li
AIMS: To investigate the efficacy of electroacupuncture (EA) alleviation of acute visceral hyperalgesia, the frequency dependence of this efficacy, and the difference in endogenous opioid pathways as underlying mechanism explaining the frequency dependence. MAIN METHODS: A visceral hyperalgesia model was established by colorectal instillation of 2% acetic acid (AA) in adult rats. EA treatment at 2Hz, 100Hz, 2/100Hz and sham EA were performed at two bilateral acupoints, ST-36 and ST-37, in the hind-limbs...
September 1, 2016: Life Sciences
https://www.readbyqxmd.com/read/27316912/delta-opioid-pharmacology-in-relation-to-alcohol-behaviors
#17
Doungkamol Alongkronrusmee, Terrance Chiang, Richard M van Rijn
Delta opioid receptors (DORs) are heavily involved in alcohol-mediated processes in the brain. In this chapter we provide an overview of studies investigating how alcohol directly impacts DOR pharmacology and of early studies indicating DOR modulation of alcohol behavior. We will offer a brief summary of the different animal species used in alcohol studies investigating DORs followed by a broader overview of the types of alcohol behaviors modulated by DORs. We will highlight a small set of studies investigating the relationship between alcohol and DORs in analgesia...
June 18, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27306612/redox-dependent-modulation-of-t-type-ca-2-channels-in-sensory-neurons-contributes-to-acute-anti-nociceptive-effect-of-substance-p
#18
Dongyang Huang, Sha Huang, Haixia Gao, Yani Liu, Jinlong Qi, Pingping Chen, Caixue Wang, Jason L Scragg, Alexander Vakurov, Chris Peers, Xiaona Du, Hailin Zhang, Nikita Gamper
AIMS: Neuropeptide substance P (SP) is produced and released by a subset of peripheral sensory neurons that respond to tissue damage (nociceptors). SP exerts excitatory effects in the central nervous system, but peripheral SP actions are still poorly understood; therefore, here, we aimed at investigating these peripheral mechanisms. RESULTS: SP acutely inhibited T-type voltage-gated Ca(2+) channels in nociceptors. The effect was mediated by neurokinin 1 (NK1) receptor-induced stimulation of intracellular release of reactive oxygen species (ROS), as it can be prevented or reversed by the reducing agent dithiothreitol and mimicked by exogenous or endogenous ROS...
August 10, 2016: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27285300/pain-regulation-of-endokinin-a-b-or-endokinin-c-d-on-chimeric-peptide-mcrt-in-mice
#19
Chunbo He, Junbin Gong, Lixia Yang, Hongwei Zhang, Shouliang Dong, Lanxia Zhou
The present study focused on the interactive pain regulation of endokinin A/B (EKA/B, the common C-terminal decapeptide in EKA and EKB) or endokinin C/D (EKC/D, the common C-terminal duodecapeptide in EKC and EKD) on chimeric peptide MCRT (YPFPFRTic-NH2, based on YPFP-NH2 and PFRTic-NH2) at the supraspinal level in mice. Results demonstrated that the co-injection of nanomolar EKA/B and MCRT showed moderate regulation, whereas 30 pmol EKA/B had no effect on MCRT. The combination of EKC/D and MCRT produced enhanced antinociception, which was nearly equal to the sum of the mathematical values of single EKC/D and MCRT...
September 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27272042/characterisation-of-the-novel-mixed-mu-nop-peptide-ligand-dermorphin-n-ofq-deno
#20
Mark F Bird, Maria Camilla Cerlesi, Mark Brown, Davide Malfacini, Vanessa Vezzi, Paola Molinari, Laura Micheli, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Remo Guerrini, Girolamo Calò, David G Lambert
INTRODUCTION: Opioid receptors are currently classified as Mu (μ), Delta (δ), Kappa (κ) plus the opioid related nociceptin/orphanin FQ (N/OFQ) peptide receptor (NOP). Despite compelling evidence for interactions and benefits of targeting more than one receptor type in producing analgesia, clinical ligands are Mu agonists. In this study we have designed a Mu-NOP agonist named DeNo. The Mu agonist component is provided by dermorphin, a peptide isolated from the skin of Phyllomedusa frogs and the NOP component by the endogenous agonist N/OFQ...
2016: PloS One
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