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Serotonergic receptors AND pain

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https://www.readbyqxmd.com/read/28533557/the-developmental-emergence-of-differential-brainstem-serotonergic-control-of-the-sensory-spinal-cord
#1
F Schwaller, A H Kanellopoulos, M Fitzgerald
Descending connections from brainstem nuclei are known to exert powerful control of spinal nociception and pain behaviours in adult mammals. Here we present evidence that descending serotonergic fibres not only inhibit nociceptive activity, but also facilitate non-noxious tactile activity in the healthy adult rat spinal dorsal horn via activation of spinal 5-HT3 receptors (5-HT3Rs). We further show that this differential serotonergic control in the adult emerges from a non-modality selective system in young rats...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28499245/anti-hyperalgesic-effect-of-lippia-grata-leaf-essential-oil-complexed-with-%C3%AE-cyclodextrin-in-a-chronic-musculoskeletal-pain-animal-model-complemented-with-a-molecular-docking-and-antioxidant-screening
#2
Pollyana S Siqueira-Lima, Renan G Brito, Heitor G Araújo-Filho, Priscila L Santos, Angélica Lucchesi, Adriano A S Araújo, Paula P Menezes, Luciana Scotti, Marcus T Scotti, Irwin R A Menezes, Henrique D M Coutinho, Gokhan Zengin, Abdurrahman Aktumsek, Angelo R Antoniolli, Lucindo J Quintans-Júnior, Jullyana S S Quintans
BACKGROUND: Due to its unclear pathophysiology, the pharmacological treatment of fibromyalgia is a challenge for researchers. Studies using medicinal plants, such as those from the genus Lippia, complexed with cyclodextrins (CDs) have shown innovative results. OBJECTIVE: The present research intended to evaluate the effect of an inclusion complex containing β-cyclodextrin (βCD) inclusion complex with Lippia grata (LG) essential oil in a chronic musculoskeletal pain model, its central activity and its possible interaction with neurotransmitters involved in pain...
May 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28387936/the-plasticity-of-descending-controls-in-pain-translational-probing
#3
Kirsty Bannister, A H Dickenson
Descending controls, comprising pathways that originate in midbrain and brainstem regions and project onto the spinal cord, have long been recognized as key links in the multiple neural networks that interact to produce the overall pain experience. There is clear evidence from preclinical and clinical studies that both peripheral and central sensitisation play important roles in determining the level of pain perceived. Much emphasis has been put on spinal cord mechanisms in central excitability, but it now becoming clear that spinal hyperexcitability can be regulated by descending pathways from the brain that originate from predominantly noradrenergic and serotonergic systems...
April 7, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28287401/prostaglandin-mediated-inhibition-of-serotonin-signaling-controls-the-affective-component-of-inflammatory-pain
#4
Anand Kumar Singh, Joanna Zajdel, Elahe Mirrasekhian, Nader Almoosawi, Isabell Frisch, Anna M Klawonn, Maarit Jaarola, Michael Fritz, David Engblom
Pain is fundamentally unpleasant and induces a negative affective state. The affective component of pain is mediated by circuits that are distinct from those mediating the sensory-discriminative component. Here, we have investigated the role of prostaglandins in the affective dimension of pain using a rodent pain assay based on conditioned place aversion to formalin injection, an inflammatory noxious stimulus. We found that place aversion induced by inflammatory pain depends on prostaglandin E2 that is synthesized by cyclooxygenase 2 in neural cells...
April 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28282362/gene-to-gene-interactions-regulate-endogenous-pain-modulation-in-fibromyalgia-patients-and-healthy-controls-antagonistic-effects-between-opioid-and-serotonin-related-genes
#5
Jeanette Tour, Monika Löfgren, Kaisa Mannerkorpi, Björn Gerdle, Anette Larsson, Annie Palstam, Indre Bileviciute-Ljungar, Jan Bjersing, Martin Ingvar, Malin Ernberg, Martin Schalling, Eva Kosek
Chronic pain is associated with dysfunctional endogenous pain modulation, involving both central opioid and serotonergic (5-HT) signaling. Fibromyalgia (FM) is a chronic pain syndrome, characterized by widespread musculoskeletal pain and reduced exercise-induced hypoalgesia (EIH). In this study, we assessed the effects of three functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls (HC). Subjects were genotyped regarding the mu-opioid receptor (OPRM1) gene (rs1799971), the serotonin transporter (5-HTT) gene (5-HTTLPR/rs25531) and the serotonin-1a receptor (5-HT1a) gene (rs6296)...
March 7, 2017: Pain
https://www.readbyqxmd.com/read/28154332/a-new-pain-regulatory-system-via-the-brain-long-chain-fatty-acid-receptor-gpr40-ffa1-signal
#6
REVIEW
Kazuo Nakamoto
 An increasingly large number of pharmacological and physiological works on fatty acids have shown that the functional properties of fatty acids are regulated by the amount of individual fatty acid intake and the distribution of fatty acids among organs. Recently, it has been determined that G-protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFA1) is activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). GPR40/FFA1 is mainly expressed in the β cell of the pancreas, spinal cord and brain...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28074005/synergistic-regulation-of-serotonin-and-opioid-signaling-contributes-to-pain-insensitivity-in-nav1-7-knockout-mice
#7
Jörg Isensee, Leonhardt Krahé, Katharina Moeller, Vanessa Pereira, Jane E Sexton, Xiaohui Sun, Edward Emery, John N Wood, Tim Hucho
Genetic loss of the voltage-gated sodium channel Nav1.7 (Nav1.7(-/-)) results in lifelong insensitivity to pain in mice and humans. One underlying cause is an increase in the production of endogenous opioids in sensory neurons. We analyzed whether Nav1.7 deficiency altered nociceptive heterotrimeric guanine nucleotide-binding protein-coupled receptor (GPCR) signaling, such as initiated by GPCRs that respond to serotonin (pronociceptive) or opioids (antinociceptive), in sensory neurons. We found that the nociceptive neurons of Nav1...
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28053243/descending-antinociception-induced-by-secondary-somatosensory-cortex-stimulation-in-experimental-neuropathy-role-of-the-medullospinal-serotonergic-pathway
#8
Boriss Sagalajev, Hanna Viisanen, Hong Wei, Antti Pertovaara
Stimulation of the secondary somatosensory cortex (S2) has attenuated pain in humans and inflammatory nociception in animals. Here we studied S2 stimulation-induced antinociception and its underlying mechanisms in an experimental animal model of neuropathy induced by spinal nerve ligation (SNL). Effect of S2 stimulation on heat-evoked limb withdrawal latency was assessed in lightly anesthetized rats that were divided into three groups based on prior surgery and monofilament testing before induction of anesthesia: 1) sham-operated group and 2) hypersensitive and 3) nonhypersensitive (mechanically) SNL groups...
March 1, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28025094/serotonergic-mechanisms-of-trigeminal-meningeal-nociception-implications-for-migraine-pain
#9
Erkan Kilinc, Cindy Guerrero-Toro, Andrey Zakharov, Carmela Vitale, Max Gubert-Olive, Ksenia Koroleva, Arina Timonina, Liliana L Luz, Irina Shelukhina, Raisa Giniatullina, Fatma Tore, Boris V Safronov, Rashid Giniatullin
Serotonergic mechanisms play a central role in migraine pathology. However, the region-specific effects of serotonin (5-HT) mediated via multiple types of receptors in the nociceptive system are poorly understood. Using extracellular and patch-clamp recordings, we studied the action of 5-HT on the excitability of peripheral and central terminals of trigeminal afferents. 5-HT evoked long-lasting TTX-sensitive firing in the peripheral terminals of meningeal afferents, the origin site of migraine pain. Cluster analysis revealed that in majority of nociceptive fibers 5-HT induced either transient or persistent spiking activity with prevailing delta and theta rhythms...
December 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27983993/lentiviral-vector-driven-inhibition-of-5-ht-synthesis-in-b3-bulbo-spinal-serotonergic-projections-consequences-on-nociception-inflammatory-and-neuropathic-pain-in-rats
#10
Anne Gautier, Hanady El Ouaraki, Natacha Bazin, Soha Salam, Guilan Vodjdani, Sylvie Bourgoin, Sophie Pezet, Jean-François Bernard, Michel Hamon
Although it is well established that bulbo-spinal serotonergic projections contribute to pain control mechanisms, whether they exert anti- or pro-nociceptive modulations is still a matter of debate. In order to reappraise the role of 5-HT in descending controls, we used RNA interference to selectively inhibit 5-HT synthesis in B3 neurons and assess resulting changes in nociception. Rats were injected into the bulbar B3 group with a recombinant lentiviral vector, LV-shTPH2, encoding RNA interfering with tryptophan hydroxylase 2 expression...
February 2017: Experimental Neurology
https://www.readbyqxmd.com/read/27916764/serotonergic-system-does-not-contribute-to-the-hypothermic-action-of-acetaminophen
#11
Akihiro Fukushima, Wakana Sekiguchi, Kizuku Mamada, Yumi Tohma, Hideki Ono
Acetaminophen (AcAP), a widely-used antipyretic and analgesic drug, has been considered to exert its effects via central mechanisms, and many studies have demonstrated that the analgesic action of AcAP involves activation of the serotonergic system. Although the serotonergic system also plays an important role in thermoregulation, the contribution of serotonergic activity to the hypothermic effect of AcAP has remained unclear. In the present study, we examined whether the serotonergic system is involved in AcAP-induced hypothermia...
February 1, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27891620/modulation-of-formalin-induced-pain-related-behaviour-by-clonidine-and-yohimbine-in-the-speke-s-hinged-tortoise-kiniskys-spekii
#12
C M Makau, P K Towett, K S P Abelson, T I Kanui
The study was designed to investigate the involvement of noradrenergic and serotonergic receptor systems in the modulation of formalin-induced pain-related behaviour in the Speke's hinged tortoise. Intradermal injection of 100 μL of formalin at a dilution of 12.5% caused pain-related behaviour (hindlimb withdrawal) that lasted for a mean time of 19.28 min (monophasic response). Intrathecal administration of clonidine (α2 -adrenergic receptor agonist) and yohimbine (α2 -adrenergic receptor antagonist) at a dose of 40 μg/kg and 37...
November 27, 2016: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27825384/inhibiting-the-proton-pump-mechanisms-benefits-harms-and-questions
#13
Jeffrey K Aronson
Inhibition of the H(+)/K(+)-adenosine triphosphatase (the proton pump) is the final common mechanistic pathway in reducing gastric acid secretion pharmacologically. Proton pump inhibitors are widely used in upper gastrointestinal diseases, including gastric and duodenal ulcers, eradication of Helicobacter pylori in combination with antibiotics, gastroesophageal reflux disease, Zollinger-Ellison syndrome, eosinophilic esophagitis, and prevention of non-steroidal anti-inflammatory drug-induced peptic ulceration...
November 9, 2016: BMC Medicine
https://www.readbyqxmd.com/read/27726068/newest-drugs-for-chronic-unexplained-nausea-and-vomiting
#14
REVIEW
William L Hasler
Chronic unexplained nausea and vomiting (CUNV) refers to a symptom complex defined by nausea and/or vomiting with normal diagnostic testing, including anatomic assessments (including upper endoscopy) and measures of upper gut function (e.g., gastric emptying testing). Nausea and vomiting in this condition are postulated to result from aberrant peripheral or central neurohumoral activity. A substantial subset of patients satisfies this diagnosis as more than half of individuals referred for scintigraphic testing exhibit normal gastric emptying rates...
December 2016: Current Treatment Options in Gastroenterology
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
#15
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/27616344/5-hydroxytryptamine2a-2c-receptors-of-nucleus-raphe-magnus-and-gigantocellularis-paragigantocellularis-pars-%C3%AE-reticular-nuclei-modulate-the-unconditioned-fear-induced-antinociception-evoked-by-electrical-stimulation-of-deep-layers-of-the-superior-colliculus
#16
Ricardo de Oliveira, Rithiele Cristina de Oliveira, Luiz Luciano Falconi-Sobrinho, Raimundo da Silva Soares, Norberto Cysne Coimbra
The electrical stimulation of the dorsolateral columns of the periaquedutal grey matter (dlPAG) or deep layers of the superior colliculus (dlSC) evokes defensive behaviours followed by an antinociceptive response. Monoaminergic brainstem reticular nuclei are suggested to comprise the endogenous pain modulatory system. The aim of the present work was to investigate the role played by 5-HT2 subfamily of serotonergic receptors of the nucleus raphe magnus (NRM) and the gigantocellularis/paragigantocellularis pars α reticular nuclei (Gi/PGiα) in the elaboration of instinctive fear-induced antinociception elicited by electrical stimulation of dlPAG or of dlSC...
January 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/27600945/the-%C3%AE-1-opioid-receptor-and-5-ht2a-and-5ht2c-serotonergic-receptors-of-the-locus-coeruleus-are-critical-in-elaborating-hypoalgesia-induced-by-tonic-and-tonic-clonic-seizures
#17
Renato Leonardo de Freitas, Priscila Medeiros, Juliana Almeida da Silva, Rithiele Cristina de Oliveira, Ricardo de Oliveira, Farhad Ullah, Asmat Ullah Khan, Norberto Cysne Coimbra
It has been proposed that the post-ictal state is associated with the expression of hypoalgesia. It is clear that the projections among the periaqueductal gray matter (PAG), dorsal raphe nucleus (DRN) and locus coeruleus (LC) play a role in pain management. These mesencephalic structures have direct reciprocal opioid and monoaminergic projections to the LC that can possibly modulate post-ictal hypoalgesia. The goal of this study was to examine if LC-opioid and serotonergic/noradrenergic mechanisms signal the post-ictal hypoalgesic responses to tonic-clonic seizures produced by intraperitoneal administration of pentylenetetrazole (PTZ at 64mg/kg), causing an ionophore γ-aminobutyric acid (GABA)-mediated Cl(-) influx antagonism...
November 12, 2016: Neuroscience
https://www.readbyqxmd.com/read/27570173/zerumbone-alleviates-chronic-constriction-injury-induced-allodynia-and-hyperalgesia-through-serotonin-5-ht-receptors
#18
Jasmine Siew Min Chia, Ahmad Akira Omar Farouk, Azam Shah Mohamad, Mohd Roslan Sulaiman, Enoch Kumar Perimal
Zerumbone, a bioactive sesquiterpene isolated from Zingiber zerumbet (Smith), has shown to exert antiallodynic and antihyperalgesic effects in neuropathic pain mice model in our recent study. The mechanism through which zerumbone alleviates neuropathic pain has yet to be elucidated. Thus, this study aimed to determine whether the serotonergic system, part of the descending pain modulation pathway, contributes to the antineuropathic effect of zerumbone. Participation of the serotonergic system in zerumbone-induced antiallodynia and antihyperalgesia was assessed using Dynamic Plantar Aesthesiometer von Frey test and Hargreaves plantar test respectively in chronic-constriction injury mice model...
October 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27449278/the-potential-role-of-serotonergic-mechanisms-in-the-spinal-oxytocin-induced-antinociception
#19
Beatriz Godínez-Chaparro, Guadalupe Martínez-Lorenzana, Javier Rodríguez-Jiménez, Alfredo Manzano-García, Gerardo Rojas-Piloni, Miguel Condés-Lara, Abimael González-Hernández
The role of oxytocin (OXT) in pain modulation has been suggested. Indeed, hypothalamic paraventricular nuclei (PVN) electrical stimuli reduce the nociceptive neuronal activity (i.e., neuronal discharge associated with activation of Aδ- and C-fibers) of the spinal dorsal horn wide dynamic range (WDR) cells and nociceptive behavior. Furthermore, raphe magnus nuclei lesion reduces the PVN-induced antinociception, suggesting a functional interaction between the OXT and the serotoninergic system. The present study investigated in Wistar rats the potential role of spinal serotonergic mechanisms in the OXT- and PVN-induced antinociception...
December 2016: Neuropeptides
https://www.readbyqxmd.com/read/27416108/inhaled-drug-therapy-development-for-the-treatment-of-migraine
#20
REVIEW
Abigail L Chua, Stephen Silberstein
INTRODUCTION: The inhalation of substances, both medicinally and recreationally, is a commonly used method of drug administration but has been underutilized in the treatment of neurologic disorders such as migraine. Three drugs have been studied as potential inhalable treatments for acute migraine: dihydroergotamine (MAP0004), prochlorperazine (Staccato prochlorperazine), and loxapine (Staccato loxapine). AREAS COVERED: This review discusses the available literature describing the pharmacokinetics, tolerability and efficacy of MAP0004, Staccato prochlorperazine and Staccato loxapine, including data from Phase II and Phase III clinical trials...
September 2016: Expert Opinion on Pharmacotherapy
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