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Serotonergic receptors AND pain

Justin N Siemian, Kaixuan Wang, Yanan Zhang, Jun-Xu Li
BACKGROUND AND PURPOSE: Although studies have established the antinociceptive efficacies of imidazoline I2 receptor (I2 R) agonists, its exact post-receptor mechanism remains unknown. This study tested the hypothesis that monoaminergic transmission is critical for I2 R agonist-induced antinociception. EXPERIMENTAL APPROACH: The von Frey filament test was used to examine the antinociceptive effects of the I2 R agonists 2-BFI and CR4056 on chronic constriction injury (CCI)-induced neuropathic pain or complete Freund's adjuvant (CFA)-induced inflammatory pain in rats...
February 16, 2018: British Journal of Pharmacology
Renan G Brito, Lynn A Rasmussen, Kathleen A Sluka
Introduction: It is generally believed that exercise produces its effects by activating central opioid receptors; there are little data that support this claim. The periaqueductal gray (PAG) and rostral ventromedial medulla (RVM) are key nuclei in opioid-induced analgesia, and opioids interact with serotonin to produce analgesia. Objectives: The purpose was to examine central inhibitory mechanisms involved in analgesia produced by wheel running. Methods: C57/Black6 mice were given access to running wheels in their home cages before induction of chronic muscle hyperalgesia and compared with those without running wheels...
September 2017: Pain Reports (Baltimore, Md.)
Soo-Hyun Park, Jae-Ryeong Lee, Sang-Pil Jang, Seyung-Hwan Park, Hee-Jung Lee, Jung-Woo Hong, Hong-Won Suh
In the present study, the antinociceptive profiles of oxyntomodulin were examined in ICR mice. Oxyntomodulin administered intrathecally (i.t.) and intracerebroventricularly (i.c.v.) (from 1 to 5μg/5μl) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Moreover, cumulative response time of nociceptive behaviors induced by intraplantar formalin injection was reduced by i.t. or i.c.v. treatment with oxyntomodulin during the second, but not the first phase...
January 20, 2018: Neuropeptides
B Sagalajev, H Wei, Z Chen, I Albayrak, A Koivisto, A Pertovaara
Earlier studies indicate that the central nucleus of the amygdala (CeA) contributes to neuropathic pain. Here we studied whether amygdaloid administration of antioxidants or antagonists of TRPA1 that is among ion channels activated by oxidative stress attenuates nociceptive or affective pain in experimental neuropathy, and whether this effect involves amygdaloid astrocytes or descending serotonergic pathways acting on the spinal 5-HT1A receptor. The experiments were performed in rats with spared nerve injury (SNI)...
December 20, 2017: Neuroscience
Aitziber Mendiguren, Erik Aostri, Joseba Pineda
The cannabinoid system is composed of Gi/o protein-coupled cannabinoid type 1 receptor (CB1 ) and cannabinoid type 2 (CB2 ) receptor and endogenous compounds. The CB1 receptor is widely distributed in the central nervous system (CNS) and it is involved in the regulation of common physiological functions. At the neuronal level, the CB1 receptor is mainly placed at GABAergic and glutamatergic axon terminals, where it modulates excitatory and inhibitory synapses. To date, the involvement of CB2 receptor in the regulation of neurotransmission in the CNS has not been clearly shown...
January 1, 2018: Life Sciences
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
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
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...
January 2018: Experimental Neurology
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
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
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
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
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
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
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
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
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
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
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
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
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