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Serotonergic receptors AND pain

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https://www.readbyqxmd.com/read/29126856/nlx-112-a-highly-selective-5-ht1a-receptor-agonist-effects-on-body-temperature-and-plasma-corticosterone-levels-in-rats
#1
A Newman-Tancredi, R Depoortère, E Carilla-Durand, J P Tarayre, M Kleven, W Koek, L Bardin, M A Varney
NLX-112 (a.k.a. F13640 or befiradol), exhibits nanomolar affinity, exceptional selectivity and high agonist efficacy at 5-hydroxytryptamine 5-HT1A receptors. It possesses marked activity in a variety of animal models of depression, pain and L-DOPA-induced dyskinesia. However, its influence on translational biomarkers of central 5-HT1A receptor activation has not been previously described. Here, we report on the activity, in rats, of NLX-112 to increase plasma corticosterone levels and produce hypothermia, two responses which are also elicited by 5-HT1A receptor agonists in humans...
November 7, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29054049/individual-variability-in-clinical-effect-and-tolerability-of-opioid-analgesics-importance-of-drug-interactions-and-pharmacogenetics
#2
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/28993250/monoaminergic-descending-pathways-contribute-to-modulation-of-neuropathic-pain-by-increasing-intensity-treadmill-exercise-after-peripheral-nerve-injury
#3
Victor M Lopez-Alvarez, Maria Puigdomenech, Xavier Navarro, Stefano Cobianchi
This study characterizes the impact of increasing-intensity treadmill exercise (iTR) on noradrenergic (NE) and serotonergic (5HT) modulation of neuropathic pain. Following sciatic nerve transection and repair (SNTR) rats developed significant mechanical and thermal hyperalgesia that was partially prevented by iTR performed during the first 2weeks after injury. Marked decrease in the expression of 5HT2A and α1A and β-, but not α2A adrenergic receptors in the spinal cord dorsal horn was associated to SNTR and recovered by iTR, particularly in lamina II...
October 7, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28874746/rgma-inhibition-with-human-monoclonal-antibodies-promotes-regeneration-plasticity-and-repair-and-attenuates-neuropathic-pain-after-spinal-cord-injury
#4
Andrea J Mothe, Nardos G Tassew, Alirezha P Shabanzadeh, Romeo Penheiro, Robin J Vigouroux, Lili Huang, Christine Grinnell, Yi-Fang Cui, Emma Fung, Philippe P Monnier, Bernhard K Mueller, Charles H Tator
Traumatic spinal cord injury (SCI) causes a cascade of degenerative events including cell death, axonal damage, and the upregulation of inhibitory molecules which prevent regeneration and limit recovery. Repulsive guidance molecule A (RGMa) is a potent neurite growth inhibitor in the central nervous system, exerting its repulsive activity by binding the Neogenin receptor. Here, we show for the first time that inhibitory RGMa is markedly upregulated in multiple cell types after clinically relevant impact-compression SCI in rats, and importantly, also in the injured human spinal cord...
September 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28856708/degeneration-of-serotonin-neurons-triggers-spasticity-in-amyotrophic-lateral-sclerosis
#5
Hajer El Oussini, Jelena Scekic-Zahirovic, Pauline Vercruysse, Christine Marques, Sylvie Dirrig-Grosch, Stéphane Dieterlé, Gina Picchiarelli, Jérôme Sinniger, Caroline Rouaux, Luc Dupuis
OBJECTIVE: Spasticity occurs in a wide range of neurological diseases, including neurodegenerative diseases, after trauma, and after stroke, and is characterized by increased reflexes leading to muscle hypertonia. Spasticity is a painful symptom and can severely restrict everyday life, but might also participate in maintaining a low level of motor function in severely impaired patients. Constitutive activity of the serotonin receptors 5-HT2B/C is required for the development of spasticity after spinal cord injury and during amyotrophic lateral sclerosis (ALS)...
September 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28763302/intramuscularly-injected-neurotropin-reduced-muscular-mechanical-hyperalgesia-induced-by-repeated-cold-stress-in-rats
#6
Teruaki Nasu, Shiori Murase, Yoshiko Takeda-Uchimura, Kazue Mizumura
An extract of rabbit skin inflamed by inoculation with the vaccinia virus, neurotropin [by intravenous, oral, and intramuscular (i.m.) administration], has been used in China and Japan for the treatment of chronic pain. In this study, we investigated the analgesic mechanism of i.m. neurotropin. Rats were exposed to repeated cold stress, and muscular mechanical hyperalgesia was evaluated by measuring the withdrawal threshold of the gastrocnemius muscle using Randall-Selitto apparatus. I.m. but not subcutaneous, neurotropin dose dependently reduced the repeated cold stress-induced muscular mechanical hyperalgesia for 3 h, but it had no effect in normal rats...
July 31, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28736332/5-hydroxytryptamine-2a-receptors-of-the-dorsal-raphe-nucleus-mediate-panic-like-behaviours-and-fear-induced-antinociception-elicited-by-neuronal-activation-in-the-central-nucleus-of-the-inferior-colliculus
#7
Raimundo da Silva Soares, Luiz Luciano Falconi-Sobrinho, Tayllon Dos Anjos-Garcia, Norberto Cysne Coimbra
It has been established that chemical stimulation of the inferior colliculus (IC) of laboratory animals evokes fear-related defensive responses, which are considered panic attack-like behaviours. In addition, there is evidence that defensive reactions provoked by chemical stimulation of midbrain tectum neurons may induce an antinociceptive response. Morphologically, the IC receives projections from other mesencephalic structures, such as the dorsal raphe nucleus (DRN), a region rich in serotonergic neurons that play a critical role in the control of defensive behaviours...
July 20, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28730896/cannabinoid-hyperemesis-syndrome-potential-mechanisms-for-the-benefit-of-capsaicin-and-hot-water-hydrotherapy-in-treatment
#8
John R Richards, Jeff M Lapoint, Guillermo Burillo-Putze
INTRODUCTION: Cannabinoid hyperemesis syndrome is a clinical disorder that has become more prevalent with increasing use of cannabis and synthetic cannabinoids, and which is difficult to treat. Standard antiemetics commonly fail to alleviate the severe nausea and vomiting characteristic of the syndrome. Curiously, cannabinoid hyperemesis syndrome patients often report dramatic relief of symptoms with hot showers and baths, and topical capsaicin. OBJECTIVES: In this review, we detail the pharmacokinetics and pharmacodynamics of capsaicin and explore possible mechanisms for its beneficial effect, including activation of transient receptor potential vanilloid 1 and neurohumoral regulation...
July 21, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28730894/low-5-ht1b-receptor-binding-in-the-migraine-brain-a-pet-study
#9
Marie Deen, Hanne D Hansen, Anders Hougaard, Sofi da Cunha-Bang, Martin Nørgaard, Claus Svarer, Sune H Keller, Carsten Thomsen, Messoud Ashina, Gitte M Knudsen
Background The pathophysiology of migraine may involve dysfunction of serotonergic signaling. In particular, the 5-HT1B receptor is considered a key player due to the efficacy of 5-HT1B receptor agonists for treatment of migraine attacks. Aim To examine the cerebral 5-HT1B receptor binding in interictal migraine patients without aura compared to controls. Methods Eighteen migraine patients, who had been migraine free for >48 hours, and 16 controls were scanned after injection of the 5-HT1B receptor specific radioligand [(11)C]AZ10419369 for quantification of cerebral 5-HT1B receptor binding...
January 1, 2017: Cephalalgia: An International Journal of Headache
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
#10
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/28655928/brain-activity-changes-in-a-macaque-model-of-oxaliplatin-induced-neuropathic-cold-hypersensitivity
#11
Kazuaki Nagasaka, Kazunori Yamanaka, Shinya Ogawa, Hiroyuki Takamatsu, Noriyuki Higo
The antineoplastic agent oxaliplatin induces a painful peripheral neuropathy characterized by an acute cold hypersensitivity. There is a lack of effective treatments to manage oxaliplatin-induced cold hypersensitivity which is due, in part, to a lack of understanding of the pathophysiology of oxaliplatin-induced cold hypersensitivity. Thus, brain activity in oxaliplatin-treated macaques was examined using functional magnetic resonance imaging (fMRI). Oxaliplatin treatment reduced tail withdrawal latency to a cold (10 °C) stimulus, indicating cold hypersensitivity and increased activation in the secondary somatosensory cortex (SII) and the anterior insular cortex (Ins) was observed...
June 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28606116/characterization-of-serotonin-induced-inhibition-of-excitatory-synaptic-transmission-in-the-anterior-cingulate-cortex
#12
Zhen Tian, Manabu Yamanaka, Matteo Bernabucci, Ming-Gao Zhao, Min Zhuo
Excitatory synaptic transmission in central synapses is modulated by serotonin (5-HT). The anterior cingulate cortex (ACC) is an important cortical region for pain perception and emotion. ACC neurons receive innervation of projecting serotonergic nerve terminals from raphe nuclei, but the possible effect of 5-HT on excitatory transmission in the ACC has not been investigated. In the present study, we investigated the role of 5-HT on glutamate neurotransmission in the ACC slices of adult mice. Bath application of 5-HT produced dose-dependent inhibition of evoked excitatory postsynaptic currents (eEPSCs)...
June 12, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28590304/antinociceptive-effect-of-epicatechin-in-inflammatory-and-neuropathic-pain-in-rats
#13
Geovanna N Quiñonez-Bastidas, Jorge B Pineda-Farias, Francisco J Flores-Murrieta, Juan Rodríguez-Silverio, Juan G Reyes-García, Beatriz Godínez-Chaparro, Vinicio Granados-Soto, Héctor I Rocha-González
The aim of this study was to investigate the antinociceptive potential of (-)-epicatechin and the possible mechanisms of action involved in its antinociceptive effect. The carrageenan and formalin tests were used as inflammatory pain models. A plethysmometer was used to measure inflammation and L5/L6 spinal nerve ligation as a neuropathic pain model. Oral (-)-epicatechin reduced carrageenan-induced inflammation and nociception by about 59 and 73%, respectively, and reduced formalin- induced and nerve injury-induced nociception by about 86 and 43%, respectively...
June 5, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/28533557/the-developmental-emergence-of-differential-brainstem-serotonergic-control-of-the-sensory-spinal-cord
#14
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
#15
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...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28387936/the-plasticity-of-descending-controls-in-pain-translational-probing
#16
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 recognised 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 is now becoming clear that spinal hyperexcitability can be regulated by descending pathways from the brain that originate from predominantly noradrenergic and serotonergic systems...
July 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28287401/prostaglandin-mediated-inhibition-of-serotonin-signaling-controls-the-affective-component-of-inflammatory-pain
#17
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
#18
Jeanette Tour, Monika Löfgren, Kaisa Mannerkorpi, Björn Gerdle, Anette Larsson, Annie Palstam, Indre Bileviciute-Ljungar, Jan Bjersing, Ingvar Martin, 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 3 functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls. 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)...
July 2017: Pain
https://www.readbyqxmd.com/read/28154332/a-new-pain-regulatory-system-via-the-brain-long-chain-fatty-acid-receptor-gpr40-ffa1-signal
#19
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
#20
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
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