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Rose Cairns, Andrea L Schaffer, Nicole Ryan, Sallie-Anne Pearson, Nicholas A Buckley
BACKGROUND AND AIMS: Pregabalin is a gamma-aminobutyric acid (GABA) analogue, used to treat neuropathic pain and epilepsy. Pregabalin was registered in Australia in 2005, and publically subsidised in 2013. We aimed to describe Australian patterns of pregabalin use and intentional poisoning, and identify people potentially at high risk of misuse. DESIGN AND SETTING: Population-based retrospective cohort study of dispensings in the 10% sample of Australian Pharmaceutical Benefits Scheme (July 2012-February 2017); intentional poisoning calls to New South Wales Poisons Information Centre (NSWPIC) (2004-2016); intentional poisonings in two Australian toxicology service databases; poisoning fatalities in NSW coronial records (2005-2016)...
August 11, 2018: Addiction
Lakshmi Rajagopal, Mei Huang, Eric Michael, Sunoh Kwon, Herbert Y Meltzer
GABAergic drugs are of interest for the treatment of anxiety, depression, bipolar disorder, pain, cognitive impairment associated with schizophrenia (CIAS), and other neuropsychiatric disorders. Some evidence suggests that TPA-023, (7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b] pyridazine), a GABAA α2,3 subtype-selective GABAA partial agonist and α1/5 antagonist, and the neurosteroid, pregnenolone sulfate, a GABAA antagonist, may improve CIAS in pilot clinical trials...
July 23, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Mohammed Zacky Ariffin, Khairunisa Mohamad Ibrahim, Andy Thiam-Huat Lee, Rui Zhi Lee, Shou Yu Poon, Hwai Kit Thong, Eugene Hern Choon Liu, Chian-Ming Low, Sanjay Khanna
The present study explored the role of the medial septal region (MS) in experimental neuropathic pain. For the first time, we found that the MS sustains nociceptive behaviors in rodent models of neuropathic pain, especially in the chronic constriction injury (CCI) model and the paclitaxel model of chemotherapy-induced neuropathic pain. For example, inactivation of the MS with intraseptal muscimol (2 μg/μl, 0.5 μl), a GABA mimetic, reversed peripheral hypersensitivity (PH) in the CCI model and induced place preference in a conditioned place preference task, a surrogate measure of spontaneous nociception...
August 8, 2018: Scientific Reports
Keisuke Migita, Yu Matsuzaki, Kohei Koga, Taichi Matsumoto, Kenichi Mishima, Shuji Hara, Kenji Honda
The role of the GABAB receptor in the anterior cingulate cortex (ACC) of neuropathic pain is unclear. Injection of a GABAB receptor antagonist CGP35348 into the ACC induced mechanical hypersensitivity in normal rats. Activation of the GABAB receptor injected by a GABAB receptor agonist baclofen into the ACC attenuated mechanical hypersensitivity in partial sciatic nerve ligation (PSNL) rats. Co-microinjection of CGP35348 with a muscarinic M1 receptor agonist McN-A-343 into the ACC significantly inhibited McN-A-343-induced antihypersensitivity in PSNL rats...
June 2018: Journal of Pharmacological Sciences
Abigail L Brewer, Shulin Liu, Amber V K Buhler, Donald Y Shirachi, Raymond M Quock
New pain treatments are in demand due to the pervasive nature of pain conditions. Hyperbaric oxygen (HBO2 ) has shown potential in treating pain in both clinical and preclinical settings, although the mechanism of this effect is still unknown. The aim of this study was to investigate whether the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) is involved in HBO2 -induced antinociception in the central nervous system. To accomplish this goal, pharmacological interactions between GABA drugs and HBO2 were investigated using the behavioral acetic acid abdominal constriction test...
August 2, 2018: Brain Research
Pablo Andrade, Erwin M J Cornips, Claudia Sommer, Marc A Daemen, Veerle Visser-Vandewalle, Govert Hoogland
BACKGROUND: The pathophysiology of pain in symptomatic thoracic disc herniation (TDH) patients remains poorly understood. Mere mechanical compression of the spinal cord and/or the exiting nerve root by a prolapsed disc cannot explain the pathogenesis of pain in all cases. Previous studies report a direct correlation between the levels of proinflammatory cytokines in disc biopsies and the severity of leg pain in patients with lumbar disc herniations. A similar correlation in patients with TDHs has not been investigated...
August 1, 2018: Spine Journal: Official Journal of the North American Spine Society
Diana M Roccaro-Waldmeyer, Franck Girard, Daniele Milani, Elisabetta Vannoni, Laurent Prétôt, David P Wolfer, Marco R Celio
The calcium-binding protein parvalbumin (PV) is a recognized marker of short-axon GABA-ergic neurons in the cortex and the hippocampus. However in addition, PV is expressed by excitatory, glutamatergic neurons in various areas of the brain and spinal cord. Depending on the location of these neurons, loading of their synaptic vesicles with glutamate is mediated by either of three vesicular glutamate transporters (VGlut): VGlut1, VGlut2, or VGlut3. Driven by our interest in one of these glutamatergic/PV-expressing cell clusters-the lateral hypothalamic parvafox nucleus-we investigated the functions of this population of neurons by the selective deletion of VGlut2 expression in PV-expressing cells according to the Cre/Lox-approach...
2018: Frontiers in Behavioral Neuroscience
Wuping Sun, Qian Zhou, Xiyuan Ba, Xiaojin Feng, Xuexue Hu, Xiaoe Cheng, Tao Liu, Jing Guo, Lizu Xiao, Jin Jiang, Donglin Xiong, Yue Hao, Zixian Chen, Changyu Jiang
Objective: Oxytocin (OT) is synthesized within the paraventricular nucleus and supraoptic nucleus of the hypothalamus. In addition to its role in uterine contraction, OT plays an important antinociceptive role; however, the underlying molecular mechanisms of antinociceptive role of OT remain elusive. We hypothesized that the antinociceptive effect of OT on neuropathic pain may occur via inhibition of TRPV1 activation in the spinal cord. The present study explores the antinociceptive role of OT and its mechanisms in neuropathic pain...
2018: Frontiers in Molecular Neuroscience
Pourzitaki Chryssa, Tsaousi Georgia, Papazisis Georgios, Kyrgidis Athanassios, Zacharis Constantinos, Kritis Aristeidis, Malliou Faye, Kouvelas Dimitrios
Fentanyl, a μ-opioid receptor agonist, has been studied for its neuro/psycho-pharmacological effects since its first clinical use; however, its effect on the release rate of the Central Nervous System (CNS) neurotransmitters has not been yet elucidated. In the present study the influence of fentanyl on the release rates of glutamate and GABA is investigated. Specifically, we examined the effects of intravenous (10 μg/kg) as well as intrahypothalamic (0.1nmol/min) fentanyl administration on the release rates of GABA and glutamate in the superfusate of anterior hypothalamus, under tail pinch manipulation...
September 5, 2018: European Journal of Pharmacology
Yuangang Liu, Weiji Weng, Shibin Wang, Ruimin Long, Hanwen Li, Huihui Li, Tengteng Li, Mengyi Wu
Diabetes mellitus is the most common endocrine disease worldwide; hyperglycemia is a hallmark of this disease. To alleviate the pain caused by diabetes, developing and utilizing effective diabetic drugs to maintain or recover the function of the residual β-cells is an attractive therapeutic approach. γ-aminobutyric acid (GABA) has been shown to have such effects, but it is easy to have reduced GABA activity under physiological conditions. In the present study, GABA-chitosan nanoparticles (GABA-CS NPs) were prepared, and glucose homeostasis, pancreatic β-cell protection, and anti-inflammatory effects of GABA-CS NPs were investigated in vivo...
March 31, 2018: ACS Omega
Adina Bathel, Lauren Schweizer, Philipp Stude, Benjamin Glaubitz, Niklas Wulms, Sibel Delice, Tobias Schmidt-Wilcke
BACKGROUND: Increased cortical excitability has been hypothesized to play a critical role in various neurological disorders, such as restless legs syndrome, epilepsy and migraine. Particularly for migraine, local hyperexcitability has been reported. Levels of regional excitatory and inhibitory neurotransmitters are related to cortical excitability and hence may play a role in the origin of the disease. Consequently, a mismatch of the excitatory-inhibitory neurotransmitter network might contribute to local hyperexcitability and the onset of migraine attacks...
July 17, 2018: Journal of Headache and Pain
Rosaria Greco, Chiara Demartini, Anna Maria Zanaboni, Cristina Tassorelli
BACKGROUND: Calcitonin gene related peptide (CGRP) is a key neuropeptide involved in the activation of the trigeminovascular system and it is likely related to migraine chronification. Here, we investigated the role of CGRP in an animal model that mimics the chronic migraine condition via repeated and intermittent nitroglycerin (NTG) administration. We also evaluated the modulatory effect of topiramate on this experimental paradigm. Male Sprague-Dawley rats were injected with NTG (5 mg/kg, i...
July 13, 2018: Journal of Headache and Pain
Sherifa Ahmed Hamed
OBJECTIVES: Pregabalin (PGB) is a gabapentinoid (ie, GABA analog), which has been Food and Drug Administration-approved for treatment of partial epilepsy in adults and neuropathic pain. It also has off-label uses for the treatment of generalized anxiety disorders, fibromyalgia, and tension headache and prevention of migraine. Few cases were reported with sexual dysfunctions (SDs) as adverse effects of PGB and gabapentin, and the majority were dose related (≥900 mg/d for gabapentin)...
July 2018: Clinical Neuropharmacology
Anna Bratus-Neuenschwander, Francesc Castro-Giner, Mojca Frank-Bertoncelj, Sirisha Aluri, Sandro F Fucentese, Ralph Schlapbach, Haiko Sprott
Joint pain causes significant morbidity in osteoarthritis (OA). The aetiology of joint pain in OA is not well understood. The synovial membrane as an innervated joint structure represents a potential source of peripheral pain in OA. Here we analyse, using a hypothesis-free next generation RNA sequencing, the differences in protein-coding and non-coding transcriptomes in knee synovial tissues from OA patients with high knee pain ( n = 5) compared with OA patients with low knee pain ( n = 5), as evaluated by visual analogue scale (VAS)...
July 4, 2018: Genes
Darakhshan Jabeen Haleem
Chronic pain conditions such as low back pain and osteoarthritis are the most prominent causes of disability worldwide. Morphine and other opioid drugs are the gold standard treatment for severe pain, including surgical pain, but the use of these drugs for chronic pain is limited largely because long term use of these drugs is associated with drug abuse and hyperalgesia which produces a negative impact on the treatment. Non-addictive treatments for chronic pain are, therefore, highly needed. Commonly used opioid drugs activate mu opioid receptors, resulting in an inhibition of tonic activity of nociceptive neurons...
August 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Mats De Jaeger, Lisa Goudman, Peter Van Schuerbeek, Johan De Mey, Bart Keymeulen, Raf Brouns, Maarten Moens
INTRODUCTION: With the development of new neuroimaging tools it has become possible to assess neurochemical alterations in patients experiencing chronic pain and to determine how these factors change during pharmacological treatment. The goal of this study was to examine the exact neurochemical mechanism underlying pregabalin treatment, utilizing magnetic resonance spectroscopy (1 H-MRS), in a population of patients with painful diabetic polyneuropathy (PDN), with the overall aim to ultimately objectify the clinical effect of pregabalin...
June 27, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Heinrich Wernze, Thomas Herdegen
Objective No single drug is broadly efficacious in the long-term treatment of fibromyalgia syndrome (FMS). Spironolactone is known to ameliorate mood and tension headache or migraine in women with premenstrual syndrome or clinical signs of hyperandrogenism. In a case series of women with treatment resistant FMS spironolactone was therefore added to their medication, and they were observed for at least 12 months. Methods 31 women with treatment-resistant FMS received spironolactone as add-on medication to various pain modulating drugs...
April 1, 2014: Scandinavian Journal of Pain
Dongsheng Xu, Hui Zhao, Han Gao, Huiling Zhao, Dandan Liu, Jing Li
Background Neuropathic pain is observed in patients as chemotherapeutic oxaliplatin is used to treat metastatic digestive tumors; however, the mechanisms responsible for hyperalgesia are not well understood. Chronic neuroinflammation is one of the hallmarks of pathophysiology of neuropathic pain. Since the midbrain periaqueductal gray is an important component of the descending inhibitory pathway controlling on central pain transmission, we examined the role for pro-inflammatory cytokines system of the periaqueductal gray in regulating mechanical hyperalgesia and cold hypersensitivity evoked by oxaliplatin...
January 2018: Molecular Pain
Carlo Corona, Silvia Pasini, Jin Liu, Fatou Amar, Lloyd A Greene, Michael L Shelanski
Activating Transcription Factor 4 (ATF4) has been postulated as a key regulator of learning and memory. We previously reported that specific hippocampal ATF4 downregulation causes deficits in synaptic plasticity and memory and reduction of glutamatergic functionality. Here we extend our studies to address ATF4's role in neuronal excitability. We find that long-term ATF4 knockdown in cultured rat hippocampal neurons significantly increases the frequency of spontaneous action potentials. This effect is associated with decreased functionality of metabotropic GABAB receptors (GABAB Rs)...
July 4, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
F Huang, X-Y Guan, Y Yan, W-G Fan, Y-Y You, H-W He, B Cheng
OBJECTIVE: Melatonin (MT) is a hormone mainly produced by the pineal gland. It may be involved in the regulation of nociception, the mechanisms of which remain unclear. In the present study, electrophysiological effects of MT on neurons were studied. MATERIALS AND METHODS: The cultured neurons were isolated from Sprague-Dawley rats trigeminal ganglia (TG). The neuron was voltage clamped using the whole cell patch clamp technique. We recorded resting membrane potential, action potential threshold and number, action potential duration and GABA-activated inward currents in the presence of 0...
May 2018: European Review for Medical and Pharmacological Sciences
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