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https://www.readbyqxmd.com/read/28737888/discovery-of-novel-proline-based-neuropeptide-ff-receptor-antagonists
#1
Thuy Nguyen, Ann M Decker, Tiffany L Langston, Kelly M Mathews, Justin N Siemian, Jun-Xu Li, Danni L Harris, Scott P Runyon, Yanan Zhang
The neuropeptide FF (NPFF) system has been implicated in a number of physiological processes including modulating the pharmacological activity of opioid analgesics and several other classes of drugs of abuse. In this study, we report the discovery of a novel proline scaffold with antagonistic activity at the NPFF receptors through a high throughput screening campaign using a functional calcium mobilization assay. Focused structure-activity relationship studies on the initial hit 1 have resulted in several analogs with calcium mobilization potencies in the submicromolar range and modest selectivity for the NPFF1 receptor...
July 24, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28736177/the-analgesic-effect-of-non-pharmacological-interventions-to-reduce-procedural-pain-in-preterm-neonates
#2
Kao-Hsian Hsieh, Shu-Jen Chen, Pei-Chen Tsao, Chih-Chien Wang, Ching-Feng Huang, Chien-Ming Lin, Ya-Ling Chou, Wei-Yu Chen, I-Ching Chan
BACKGROUND: Painful procedures are unavoidable in the medical care of preterm babies. The unpleasant experience during the neonatal period may contribute to hyperalgesia and poor neurodevelopment outcome later. Seeking effective interventions to reduce pain are strongly indicated for these very small premature babies. The aim of this study is to investigate if instilling breast milk (BM) or dextrose water into oral cavity can reduce the procedural pain of heel stick for preterm babies...
July 11, 2017: Pediatrics and Neonatology
https://www.readbyqxmd.com/read/28734619/fibromyalgia-prevalence-epidemiologic-profiles-and-economic-costs
#3
REVIEW
Asensi Cabo-Meseguer, Germán Cerdá-Olmedo, José Luis Trillo-Mata
Fibromyalgia is an idiopathic chronic condition that causes widespread musculoskeletal pain, hyperalgesia and allodynia. This review aims to approach the general epidemiology of fibromyalgia according to the most recent published studies, identifying the general worldwide prevalence of the disease, its basic epidemiological profiles and its economic costs, with specific interest in the Spanish and Comunidad Valenciana cases. Fibromyalgia affects, on average, 2.10% of the world's population; 2.31% of the European population; 2...
July 19, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28732764/vasculitic-peripheral-neuropathy-induced-by-ischemia-reperfusion-in-the-rat-femoral-artery-involves-activation-of-proinflammatory-signaling-pathway-in-the-sciatic-nerve
#4
Chih-Yang Chung, Yi-Wei Chang, Chun-Jen Huang, Po-Kai Wang, Hung-Chieh Wan, Yi-Ying Lin, Ming-Chang Kao
Ischemia-reperfusion (IR) in the rat femoral artery has been proposed as an experimental model of vasculitic peripheral neuropathy (VPN) which presents neuropathic pain and peripheral nerve injury patterns observed clinically. This study investigates the involvement of the proinflammatory signaling pathway underlying the peripheral mechanisms of VPN. Male Sprague-Dawley rats were allocated to receive either a sham operation or IR. IR was induced by occluding the right femoral artery for 4hours followed by reperfusion periods from 0 to 72hours...
July 18, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28731926/history-of-anaesthesia-the-ketamine-story-past-present-and-future
#5
Georges Mion
: Ketamine's history begins in the 1950s in Detroit, Michigan, at Parke-Davis Laboratories. On 26 March 1956, Harold V. Maddox synthesised phencyclidine or PCP. Domino studied PCP effects in animals and in 1958, Greifenstein made the first trials of PCP in humans under the name of Sernyl. Sernyl did not cause depression of cardiovascular and respiratory functions, but elicited severe excitation with a very prolonged postoperative recovery. Because of its psychedelic effects, it became a street drug under the name of 'angel dust' and was placed on schedule II of Federal Controlled Substance Act (CSA) in 1978...
July 20, 2017: European Journal of Anaesthesiology
https://www.readbyqxmd.com/read/28730237/therapeutic-potential-of-certain-drug-combinations-on-paclitaxel-induced-peripheral-neuropathy-in-rats
#6
Cristina Elena Zbârcea, IonuŢ Cosmin Ciotu, Veronica Bild, Cornel ChiriŢă, Alexandra Mihaela Tănase, Oana Cristina Şeremet, Emil Ştefănescu, Andreea LetiŢia Arsene, Alexandra Eugenia Bastian, Floriana Elvira Ionică, Simona Negreş
BACKGROUND AND AIMS: Experimental research and clinical data support the potential combination therapy for the treatment of neuropathic pain. We aimed to investigate the analgesic effect of the following associations: gabapentin + etifoxine; tramadol + etifoxine; gabapentin + tramadol, in an experimental model of peripheral neuropathy induced by paclitaxel. MATERIALS AND METHODS: Neuropathy was induced in male Wistar rats by the daily administration of 2 mg÷kg body weight (bw) paclitaxel intraperitoneally, four days in a row...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28728819/regulation-of-piezo-channels-by-cellular-signaling-pathways
#7
I Borbiro, T Rohacs
The recently identified mechanically activated Piezo1 and Piezo2 channels play major roles in various aspects of mechanosensation in mammals, and their mutations are associated with human diseases. Recent reports show that activation of cell surface receptors coupled to heterotrimeric Gq proteins increase the sensitivity of Piezo2 channels to mechanical stimuli. Activation of the cyclic adenosine monophosphate pathway was also shown to potentiate Piezo2 channel activity. This phenomenon may play a role in mechanical allodynia or hyperalgesia during inflammation...
2017: Current Topics in Membranes
https://www.readbyqxmd.com/read/28727492/chronic-psychological-stress-seems-associated-with-elements-of-the-metabolic-syndrome-in-patients-with-ischaemic-heart-disease
#8
Natasha Bergmann, Søren Ballegaard, Jesper Krogh, Per Bech, Åke Hjalmarson, Finn Gyntelberg, Jens Faber
BACKGROUND AND OBJECTIVES: Chronic psychological stress, the metabolic syndrome (MS) and ischaemic heart disease (IHD) seem closely connected. In this study, we evaluate the association between chronic stress and elements of MS in patients with stable IHD. DESIGN: Cross-sectional cohort study. METHODS: Three hundred and fifty patients with stable IHD were included. Chronic stress was evaluated by the two questionnaires, Major Depression Inventory (MDI) and the psychological wellbeing index WHO-5, as well as by Pressure Pain Sensitivity (PPS), a physiological measure of hyperalgesia at the sternum known to be associated to elements of the chronic stress syndrome...
July 20, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28725942/l-arginine-supplementation-prevents-allodynia-and-hyperalgesia-in-painful-diabetic-neuropathic-rats-by-normalizing-plasma-nitric-oxide-concentration-and-increasing-plasma-agmatine-concentration
#9
Lusliany J Rondón, M C Farges, N Davin, B Sion, A M Privat, M P Vasson, A Eschalier, C Courteix
PURPOSE: Neuropathic pain is a common diabetic complication. It is characterized by symptoms of spontaneous and stimulus-evoked pain including hyperalgesia and allodynia. L-Arginine is a common precursor of many metabolites of biological interest, in particular, nitric oxide (NO), ornithine, and hence polyamines. In central nervous system, NO, glutamate, and polyamines share an N-methyl-D-aspartate (NMDA) receptor-mediated effect. We hypothesized that a variation in arginine metabolism caused by diabetes may contribute to development and maintenance of neuropathic pain and to the worsening of clinical and biological signs of diabetes...
July 19, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/28724917/endocannabinoids-have-opposing-effects-on-behavioral-responses-to-nociceptive-and-non-nociceptive-stimuli
#10
Torrie Summers, Brandon Hanten, Warren Peterson, Brian Burrell
The endocannabinoid system is thought to modulate nociceptive signaling making it a potential therapeutic target for treating pain. However, there is evidence that endocannabinoids have both pro- and anti-nociceptive effects. In previous studies using Hirudo verbana (the medicinal leech), endocannabinoids were found to depress nociceptive synapses, but enhance non-nociceptive synapses. Here we examined whether endocannabinoids have similar bidirectional effects on behavioral responses to nociceptive vs. non-nociceptive stimuli in vivo...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28723961/dysfunctional-gpr40-ffar1-signaling-exacerbates-pain-behavior-in-mice
#11
Kazuo Nakamoto, Fuka Aizawa, Kei Miyagi, Takuya Yamashita, Mitsumasa Mankura, Yutaka Koyama, Fumiyo Kasuya, Akira Hirasawa, Takashi Kurihara, Atsuro Miyata, Shogo Tokuyama
We previously showed that activation of G protein-coupled receptor 40/free fatty acid receptor 1 (GPR40/FFAR1) signaling modulates descending inhibition of pain. In this study, we investigated the involvement of fatty acid-GPR40/FFAR1 signaling in the transition from acute to chronic pain. We used GPR40/FFAR1-knockout (GPR40KO) mice and wild-type (WT) mice. A plantar incision was performed, and mechanical allodynia and thermal hyperalgesia were evaluated with a von Frey filament test and plantar test, respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28722815/influence-of-morphine-and-naloxone-on-pain-modulation-in-rheumatoid-arthritis-chronic-fatigue-syndrome-fibromyalgia-and-controls-a-double-blind-randomized-placebo-controlled-cross-over-study
#12
Linda Hermans, Jo Nijs, Patrick Calders, Luc De Clerck, Greta Moorkens, Guy Hans, Sofie Grosemans, Tine Roman De Mettelinge, Joanna Tuynman, Mira Meeus
BACKGROUND: Impaired pain inhibitory and enhanced pain facilitatory mechanisms are repeatedly reported in patients with central sensitization pain. However, the exact effects of frequently prescribed opioids on central pain modulation are still unknown. METHODS: A randomized, double-blind, placebo-controlled cross-over trial was carried out. Ten CFS/FM patients, 11 RA patients and 20 controls were randomly allocated to the experimental (10 mg morphine or 0.2 mg/ml Naloxone) and placebo (2 ml Aqua) group...
July 19, 2017: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/28722336/evidence-for-the-modulation-of-nociception-in-mice-by-central-mast-cells
#13
C L Kissel, K J Kovács, A A Larson
BACKGROUND: Hyperalgesia that develops following nerve ligation corresponds temporally and in magnitude with the number of thalamic mast cells located contralateral to the ligature. We tested the possibility that mast cells modulate nociception centrally, similar to their role in the periphery. METHODS: We examined the central effect of two hyperalgesic compounds that induce mast cell degranulation and of stabilized mast cells using cromolyn. RESULTS: Thermal hyperalgesia (tail flick) induced by nerve growth factor (NGF, a neurotrophic compound) and mechanical hyperalgesia (von Frey) induced by dynorphin A (1-17) (opioid compound) each correlated with the per cent of thalamic mast cells that were degranulated...
July 19, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28721090/muscle-injections-with-lidocaine-improve-resting-fatigue-and-pain-in-patients-with-chronic-fatigue-syndrome
#14
Roland Staud, Taylor Kizer, Michael E Robinson
OBJECTIVE: Patients with chronic fatigue syndrome (CFS) complain of long-lasting fatigue and pain which are not relieved by rest and worsened by physical exertion. Previous research has implicated metaboreceptors of muscles to play an important role for chronic fatigue and pain. Therefore, we hypothesized that blocking impulse input from deep tissues with intramuscular lidocaine injections would improve not only the pain but also fatigue of CFS patients. METHODS: In a double-blind, placebo-controlled study, 58 CFS patients received 20 mL of 1% lidocaine (200 mg) or normal saline once into both trapezius and gluteal muscles...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28721088/forced-exercise-attenuates-neuropathic-pain-in-chronic-constriction-injury-of-male-rat-an-investigation-of-oxidative-stress-and-inflammation
#15
Hossein Ali Safakhah, Nasroallah Moradi Kor, Atiyeh Bazargani, Ahmad Reza Bandegi, Hamid Gholami Pourbadie, Baharak Khoshkholgh-Sima, Ali Ghanbari
BACKGROUND AND OBJECTIVE: Initial peripheral/central nerve injuries, such as chronic constriction injury (CCI)/spinal cord injury, are often compounded by secondary mechanisms, including inflammation and oxidative stress, which may lead to chronic neuropathic pain characterized by hyperalgesia or allodynia. On the other hand, exercise as a behavioral and non-pharmacological treatment has been shown to alleviate chronic neuropathic pain. Therefore, this study was conducted to examine whether or not exercise reduces neuropathic pain through modifying oxidative stress and inflammation in chronic constriction injury of the sciatic nerve...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28720466/antinociceptive-effects-of-huf-101-a-fluorinated-cannabidiol-derivative
#16
Nicole R Silva, Felipe V Gomes, Miriam D Fonseca, Raphael Mechoulam, Aviva Breuer, Thiago M Cunha, Francisco S Guimarães
Cannabidiol (CBD) is a phytocannabinoid with multiple pharmacological effects and several potential therapeutic properties. Its low oral bioavailability, however, can limit its clinical use. Preliminary results indicate that fluorination of the CBD molecule increases its pharmacological potency. Here, we investigated whether HUF-101 (3, 10, and 30mg/kg), a fluorinated CBD analogue, would induce antinociceptive effects. HUF-101 effects were compared to those induced by CBD (10, 30, and 90mg/kg) and the cannabinoid CB1/2 receptor agonist WIN55,212-2 (1, 3, and 5mg/kg)...
July 15, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28719859/-curcumin-loaded-poly-d-l-lactide-co-glycolide-nanovesicles-induce-antinociceptive-effects-and-reduce-pronociceptive-cytokine-and-bdnf-release-in-spinal-cord-after-acute-administration-in-mice
#17
Stefano Pieretti, Amalendu P Ranjan, Amalia Di Giannuario, Anindita Mukerjee, Francesca Marzoli, Rita Di Giovannandrea, Jamboor K Vishwanatha
Given the poor bioavailability of curcumin, its antinociceptive effects are produced after chronic intravenous administration of high doses, while poly (d,l-lactide-co-glycolide)-loaded vesicles (PLGA) can improve drug delivery. This paper investigates the antinociceptive effects of curcumin-loaded PLGA nanovesicles (PLGA-CUR) administered via intravenous (i.v.) or intrathecal (i.t.) routes at low and high doses. The following models of pain were used: formalin test, zymosan-induced hyperalgesia and sciatic nerve ligation inducing neuropathic allodynia and hyperalgesia...
July 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28719094/discovery-and-characterization-of-a-novel-tryptophan-hydroxylase-1-inhibitor-as-a-prodrug
#18
Hailong Shi, Yaya Cui, Yifei Qin
Serotonin (5-HT) is an important neurotransmitter and paracrine signaling molecule in the gastrointestinal tract. Two distinct tryptophan hydroxylases (TPH), TPH1 and TPH2 are the rate-limiting enzymes in the 5-HT biosynthesis process. TPH1 expression is mainly limited in the enterochromaffin cells and distributed in peripheries such as the skin and gut, while TPH2 is the predominant isoform in the CNS. In this study, mol002291 was screened as a drug-like compound from the TCM database for the inhibitor of TPH...
July 18, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28718992/melatonin-impedes-tet1-dependent-mglur5-promoter-demethylation-to-relieve-pain
#19
Ming-Chun Hsieh, Yu-Cheng Ho, Cheng-Yuan Lai, Dylan Chou, Hsueh-Hsiao Wang, Gin-Den Chen, Tzer-Bin Lin, Hsien-Yu Peng
Melatonin (N-acetyl-5-methoxytryptamine)/MT2 receptor-dependent epigenetic modification represents a novel pathway in the treatment of neuropathic pain. Because spinal ten-eleven translocation methylcytosine dioxygenase 1 (Tet1)-dependent epigenetic demethylation has recently been linked to pain hypersensitivity, we hypothesized that melatonin/MT2-dependent analgesia involves spinal Tet1-dependent demethylation. Here, we showed that spinal Tet1 gene transfer by intrathecal delivery of Tet1-encoding vectors to naïve rats produced profound and long-lasting nociceptive hypersensitivity...
July 18, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28716934/sigma-1-receptors-control-immune-driven-peripheral-opioid-analgesia-during-inflammation-in-mice
#20
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
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