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https://www.readbyqxmd.com/read/28633926/synergic-stimulation-of-serotonin-5-ht1a-receptor-and-%C3%AE-2-adrenoceptors-for-neuropathic-pain-relief-preclinical-effects-of-2-substituted-imidazoline-derivatives
#1
Lorenzo Di Cesare Mannelli, Carla Ghelardini, Laura Micheli, Fabio Del Bello, Mario Giannella, Alessandro Piergentili, Wilma Quaglia
Neuropathic pain affects millions of people causing disability and impairing quality of life. Commonly used analgesics are generally characterized by limited therapeutic outcomes. The serotonin 5-HT1A receptor and the α2 adrenergic receptors are involved in central nociceptive mechanisms with a pivotal role in the inhibitory descending pain pathway. Since their stimulation may modulate the nervous signaling altered by neuropathies, the purpose of the present research is the study of the combined activation of 5-HT1A and α2 receptors by rationally designed imidazoline ligands ((S)-1 and 2-5) in a rat model of neuropathic pain (chronic constriction injury - CCI)...
June 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28629730/synergistic-antinociceptive-effect-of-a-calcium-channel-blocker-and-a-trpv1-blocker-in-an-acute-pain-model-in-mice
#2
Manuella R Palhares, Juliana F Silva, Marcio Junior S Rezende, Duana C Santos, Cláudio A Silva-Junior, Márcia H Borges, Juliano Ferreira, Marcus V Gomez, Célio J Castro Junior
AIMS: Extensive evidence supports a role for voltage-gated calcium channels (VGCC) and TRPV1 receptors in pain transmission and modulation. We investigated the profile of analgesic interaction between Phα1β toxin (a VGCC blocker) and SB366791 (selective TRPV1 antagonist) in a model of acute pain induced by capsaicin. Changes in body temperature induced by combination regimens were also evaluated. MAIN METHODS: Isobolographic approach with a fixed dose-ratio of combined drugs was used to determine whether antinociceptive interaction of Phα1β and SB366791 are subadditive, additive or synergic...
June 16, 2017: Life Sciences
https://www.readbyqxmd.com/read/28629283/prevalence-and-correlates-of-major-depression-among-nigerian-adults-with-sickle-cell-disease
#3
Saheed O Raji, Ambrose O Lawani, Bawo O James
Objective To ascertain the current and lifetime prevalence of depression among adults with sickle cell disease and identify relevant socio-demographic and clinical correlates. Method A cross-sectional study of 205 stable adult out-patient attendees at a treatment center in southern Nigeria between April and September, 2014. A socio-demographic questionnaire, the depression module of Mini International Neuropsychiatric Interview, and the eight-item Morisky Medication Adherence Scale were administered. Categorical and continuous variables associated with a diagnosis of depression were tested using chi-squared and t-tests respectively...
July 2016: International Journal of Psychiatry in Medicine
https://www.readbyqxmd.com/read/28628911/a-carasil-patient-from-americas-with-novel-mutation-and-atypical-features-case-presentation-and-literature-review
#4
Muhammad Ibrahimi, Hiroaki Nozaki, Angelica Lee, Osamu Onodera, Raymond Reichwein, Matthew Wicklund, Mohammad El-Ghanem
OBJECTIVE: Reporting a novel mutation in the HTRA1 gene in a CARASIL patient from Americas. METHODS: Clinical presentation and neuroimaging were consistent with CARASIL. HTRA1 DNA sequencing was performed using advanced ("next generation") sequencing technology. The results revealed a homozygous missense mutation as c.616G>A (p.Gly206Arg) in the HTRA1 gene. RESULTS: A 24-year-old man with a history of chronic back pain presented with recurrent ischemic strokes...
June 21, 2017: Cerebrovascular Diseases
https://www.readbyqxmd.com/read/28627793/increased-sympathetic-outflow-induces-adaptation-to-acute-experimental-pain
#5
Lior Dayan, Uri Hochberg, Hadas Nahman-Averbuch, Silviu Brill, Jacob N Ablin, Giris Jacob
BACKGROUND: There are interrelationships between the autonomic nervous system and pain. This study aims to explore the effect of different autonomic manipulations on pain perception and modulation. METHODS: Twenty healthy subjects (10 men and 10 women, mean age 25±3) participate in this single-blinded, semi-randomized, controlled study, which included 2 study visits. Warm and heat pain thresholds, conditioned pain modulation and pain adaptation were tested before and after administration of phenylephrine, clonidine, yohimbine and saline...
June 19, 2017: Pain Practice: the Official Journal of World Institute of Pain
https://www.readbyqxmd.com/read/28625755/multilevel-engineering-of-the-upstream-module-of-aromatic-amino-acid-biosynthesis-in-saccharomyces-cerevisiae-for-high-production-of-polymer-and-drug-precursors
#6
Miguel Suástegui, Chiam Yu Ng, Anupam Chowdhury, Wan Sun, Mingfeng Cao, Emma House, Costas D Maranas, Zengyi Shao
A multilevel approach was implemented in Saccharomyces cerevisiae to optimize the precursor module of the aromatic amino acid biosynthesis pathway, which is a rich resource for synthesizing a great variety of chemicals ranging from polymer precursor, to nutraceuticals and pain-relief drugs. To facilitate the discovery of novel targets to enhance the pathway flux, we incorporated the computational tool YEASTRACT for predicting novel transcriptional repressors and OptForce strain-design for identifying non-intuitive pathway interventions...
June 15, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28625720/the-cannabinoid-system-and-pain
#7
REVIEW
Stephen G Woodhams, Victoria Chapman, David P Finn, Andrea G Hohmann, Volker Neugebauer
Chronic pain states are highly prevalent and yet poorly controlled by currently available analgesics, representing an enormous clinical, societal, and economic burden. Existing pain medications have significant limitations and adverse effects including tolerance, dependence, gastrointestinal dysfunction, cognitive impairment, and a narrow therapeutic window, making the search for novel analgesics ever more important. In this article, we review the role of an important endogenous pain control system, the endocannabinoid (EC) system, in the sensory, emotional, and cognitive aspects of pain...
June 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28624955/presynaptic-inhibition-of-nociceptive-neurotransmission-by-somatosensory-neuron-secreted-suppressors
#8
REVIEW
Kaicheng Li, Bing Cai, Changlin Li, Xu Zhang
Noxious stimuli cause pain by activating cutaneous nociceptors. The Aδ- and C-fibers of dorsal root ganglion (DRG) neurons convey the nociceptive signals to the laminae I-II of spinal cord. In the dorsal horn of spinal cord, the excitatory afferent synaptic transmission is regulated by the inhibitory neurotransmitter γ-aminobutyric acid and modulators such as opioid peptides released from the spinal interneurons, and by serotonin, norepinepherine and dopamine from the descending inhibitory system. In contrast to the accumulated evidence for these central inhibitors and their neural circuits in the dorsal spinal cord, the knowledge about the endogenous suppressive mechanisms in nociceptive DRG neurons remains very limited...
June 15, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28623618/endothelin-1-decreases-excitability-of-the-dorsal-root-ganglion-neurons-via-etb-receptor
#9
Nandkishor K Mule, Jitendra N Singh, Kunal U Shah, Anil Gulati, Shyam S Sharma
Endothelin-1 (ET-1) has been demonstrated to be a pro-nociceptive as well as an anti-nociceptive agent. However, underlying molecular mechanisms for these pain modulatory actions remain unclear. In the present study, we evaluated the ability of ET-1 to alter the nociceptor excitability using a patch clamp technique in acutely dissociated rat dorsal root ganglion (DRG) neurons. ET-1 produced an increase in threshold current to evoke an action potential (I threshold) and hyperpolarization of resting membrane potential (RMP) indicating decreased excitability of DRG neurons...
June 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28623463/hypotonicity-induced-cell-swelling-activates-trpa1
#10
Fumitaka Fujita, Kunitoshi Uchida, Yasunori Takayama, Yoshiro Suzuki, Masayuki Takaishi, Makoto Tominaga
Hypotonic solutions can cause painful sensations in nasal and ocular mucosa through molecular mechanisms that are not entirely understood. We clarified the ability of human TRPA1 (hTRPA1) to respond to physical stimulus, and evaluated the response of hTRPA1 to cell swelling under hypotonic conditions. Using a Ca(2+)-imaging method, we found that modulation of AITC-induced hTRPA1 activity occurred under hypotonic conditions. Moreover, cell swelling in hypotonic conditions evoked single-channel activation of hTRPA1 in a cell-attached mode when the patch pipette was attached after cell swelling under hypotonic conditions, but not before swelling...
June 16, 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/28623271/decoy-peptide-targeted-to-toll-il-1r-domain-inhibits-lps-and-tlr4-active-metabolite-morphine-3-glucuronide-sensitization-of-sensory-neurons
#11
Yohance M Allette, Youngsook Kim, Aaron L Randolph, Jared A Smith, Matthew S Ripsch, Fletcher A White
Accumulating evidence indicates that Toll-like receptor (TLR) signaling adapter protein interactions with Toll/Interleukin-1 Receptor (TIR) domains present in sensory neurons may modulate neuropathic pain states. Following ligand interaction with TLRs, TIR serves to both initiate intracellular signaling and facilitate recruitment of signaling adapter proteins to the intracytoplasmic domain. Although TLR TIR is central to a number of TLR signaling cascades, its role in sensory neurons is poorly understood. In this study we investigated the degree to which TLR TIR decoy peptide modified to include a TAT sequence (Trans-Activator of Transcription gene in HIV; TAT-4BB) affected LPS-induced intracellular calcium flux and excitation in sensory neurons, and behavioral changes due to TLR4 active metabolite, morphine-3-glucuronide (M3G) exposure in vivo...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622274/a-role-for-neurokinin-1-receptor-neurons-in-the-rostral-ventromedial-medulla-in-the-development-of-chronic-postthoracotomy-pain
#12
Sergey G Khasabov, Jeffrey Chi-Fei Wang, Donald A Simone, Gary R Strichartz
Thoracotomy results in chronic postoperative pain (CPTP) in half of the cases. Earlier findings in rat models of persistent post-surgical pain suggest that spinal pathways are critical for pain onset but not its maintenance. Descending systems from the brain stem modulate nociceptive transmission in the spinal cord and contribute to persistent pain, but their role in chronic postoperative pain has not been studied. Here, we ablated pronociceptive neurokinin-1 receptor (NK-1R)-expressing neurons in the rat rostral ventromedial medulla (RVM) to identify their role in CPTP...
July 2017: Pain
https://www.readbyqxmd.com/read/28621702/short-duration-physical-activity-prevents-the-development-of-activity-induced-hyperalgesia-through-opioid-and-serotoninergic-mechanisms
#13
Lucas V Lima, Josimari M DeSantana, Lynn A Rasmussen, Kathleen A Sluka, Lucas Vasconcelos Lima
Regular physical activity prevents development of chronic muscle pain through modulation of central mechanisms that involve rostral ventromedial medulla (RVM). We tested if pharmacological blockade or genetic deletion of mu-opioid receptors in physically active mice modulates excitatory and inhibitory systems in the RVM in an activity-induced hyperalgesia model. We examined response frequency to mechanical stimulation of the paw, muscle withdrawal thresholds, and expression of phosphorylation of the NR1 subunit of the NMDA receptor (p-NR1) and serotonin transporter (SERT) in the RVM...
June 8, 2017: Pain
https://www.readbyqxmd.com/read/28619476/brexanolone-sage-547-injection-in-post-partum-depression-a-randomised-controlled-trial
#14
Stephen Kanes, Helen Colquhoun, Handan Gunduz-Bruce, Shane Raines, Ryan Arnold, Amy Schacterle, James Doherty, C Neill Epperson, Kristina M Deligiannidis, Robert Riesenberg, Ethan Hoffmann, David Rubinow, Jeffrey Jonas, Steven Paul, Samantha Meltzer-Brody
BACKGROUND: Post-partum depression is a serious mood disorder in women that might be triggered by peripartum fluctuations in reproductive hormones. This phase 2 study investigated brexanolone (USAN; formerly SAGE-547 injection), an intravenous formulation of allopregnanolone, a positive allosteric modulator of γ-aminobutyric acid (GABAA) receptors, for the treatment of post-partum depression. METHODS: For this double-blind, randomised, placebo-controlled trial, we enrolled self-referred or physician-referred female inpatients (≤6 months post partum) with severe post-partum depression (Hamilton Rating Scale for Depression [HAM-D] total score ≥26) in four hospitals in the USA...
June 12, 2017: Lancet
https://www.readbyqxmd.com/read/28618292/influence-of-transcutaneous-spinal-stimulation-on-human-ltp-like-pain-amplification-a-randomized-double-blind-study-in-volunteers
#15
L M Schweizer, P K Zahn, E M Pogatzki-Zahn, W Magerl, M Tegenthoff, C H Meyer-Frießem
OBJECTIVE: Transcutaneous spinal direct current stimulation (tsDCS) has been proven to affect nociceptive signal processing. We designed a randomized, double-blind, cross-over study to investigate whether tsDCS applied before or after inducing long-term potentiation-(LTP)-like hyperalgesia may decrease nociceptive sensitivity. METHODS: In healthy volunteers, tsDCS (2.5mA, 15min) was applied to the thoracic spine prior (n=14) or immediately following (n=12) electrical high-frequency stimulation (HFS) to the thigh, inducing hyperalgesia...
May 18, 2017: Clinical Neurophysiology: Official Journal of the International Federation of Clinical Neurophysiology
https://www.readbyqxmd.com/read/28618070/morin-suppresses-astrocyte-activation-and-regulates-cytokine-release-in-bone-cancer-pain-rat-models
#16
Wei Jiang, Ying Wang, Wei Sun, Mengyuan Zhang
As inflammatory and immune responses are involved in pathophysiology of debilitating neuropathic pain, reagents that can modulate these two responses may have therapeutic potential. Morin, derived from the moraceae family of plants, benefits inflammation-related diseases, but its antinociceptive effects on cancer pain remain elusive. In the present study, we investigated antinociceptive effects of morin on bone cancer pain using a rat model, where rats were subject to implantation of Walker 256 mammary gland carcinoma cells into the tibia...
June 15, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28617566/randomized-double-blind-placebo-controlled-trial-of-n-acetylcysteine-augmentation-for-treatment-resistant-obsessive-compulsive-disorder
#17
Daniel L C Costa, Juliana B Diniz, Guaraci Requena, Marinês A Joaquim, Christopher Pittenger, Michael H Bloch, Euripedes C Miguel, Roseli G Shavitt
OBJECTIVE: To evaluate the efficacy of serotonin reuptake inhibitor (SRI) augmentation with N-acetylcysteine (NAC), a glutamate modulator and antioxidant medication, for treatment-resistant obsessive-compulsive disorder (OCD). METHODS: We conducted a randomized, double-blind, placebo-controlled, 16-week trial of NAC (3,000 mg daily) in adults (aged 18-65 years) with treatment-resistant OCD, established according to DSM-IV criteria. Forty subjects were recruited at an OCD-specialized outpatient clinic at a tertiary hospital (May 2012-October 2014)...
June 6, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28616038/electroacupuncture-at-fengchi-gb20-inhibits-calcitonin-gene-related-peptide-expression-in-the-trigeminovascular-system-of-a-rat-model-of-migraine
#18
Luo-Peng Zhao, Lu Liu, Pei Pei, Zheng-Yang Qu, Yu-Pu Zhu, Lin-Peng Wang
Most migraine patients suffer from cutaneous allodynia; however, the underlying mechanisms are unclear. Calcitonin gene-related peptide (CGRP) plays an important role in the pathophysiology of migraine, and it is therefore, a potential therapeutic target for treating the pain. In the present study, a rat model of conscious migraine, induced by repeated electrical stimulation of the superior sagittal sinus, was established and treated with electroacupuncture at Fengchi (GB20) (depth of 2-3 mm, frequency of 2/15 Hz, intensity of 0...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28615967/assessment-of-direct-analgesic-effect-of-duloxetine-for-chronic-low-back-pain-post-hoc-path-analysis-of-double-blind-placebo-controlled-studies
#19
Hiroyuki Enomoto, Shinji Fujikoshi, Jumpei Funai, Nao Sasaki, Michael H Ossipov, Toshinaga Tsuji, Levent Alev, Takahiro Ushida
BACKGROUND: Comorbid depression and depressive symptoms are common in patients with chronic low back pain (CLBP). Duloxetine is clinically effective in major depressive disorder and several chronic pain states, including CLBP. The objective of this post hoc meta-analysis was to assess direct and indirect analgesic efficacy of duloxetine for patients with CLBP in previous clinical trials. METHODS: Post hoc path analyses were conducted of 3 randomized, double-blind, clinical studies of patients receiving duloxetine or placebo for CLBP...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28615966/acute-physiological-and-electrical-accentuation-of-vagal-tone-has-no-effect-on-pain-or-gastrointestinal-motility-in-chronic-pancreatitis
#20
Jacob Juel, Christina Brock, Søren S Olesen, Adnan Madzak, Adam D Farmer, Qasim Aziz, Jens B Frøkjær, Asbjørn Mohr Drewes
BACKGROUND: The effective management of pain in chronic pancreatitis (CP) remains a therapeutic challenge. Analgesic drugs, such as opioids, and the underlying pathology can impair gut function. The autonomic nervous system influences hormone secretion and gut motility. In healthy volunteers, electrical (using noninvasive transcutaneous vagal nerve stimulation [t-VNS]) and physiological (using deep slow breathing [DSB]) modulation of parasympathetic tone results in pain attenuation and enhanced gut motility...
2017: Journal of Pain Research
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