Activation of Orexin System Facilitates Anesthesia Emergence and Pain Control
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The Hypothalamus and the Regulation of Energy Homeostasis: Lifting the Lid on a Black Box
Proceedings of the Nutrition Society (2000), 59, 385–396 385 CAB59385Signalling39612© NutritionInternationalPNSProceedings Society in body-weight 2000 homeostasisG. of the Nutrition Williams Society et (2000)0029-6651©al.385 Nutrition Society 2000 593 The hypothalamus and the regulation of energy homeostasis: lifting the lid on a black box Gareth Williams*, Joanne A. Harrold and David J. Cutler Diabetes and Endocrinology Research Group, Department of Medicine, The University of Liverpool, Liverpool L69 3GA, UK Professor Gareth Williams, fax +44 (0)151 706 5797, email [email protected] The hypothalamus is the focus of many peripheral signals and neural pathways that control energy homeostasis and body weight. Emphasis has moved away from anatomical concepts of ‘feeding’ and ‘satiety’ centres to the specific neurotransmitters that modulate feeding behaviour and energy expenditure. We have chosen three examples to illustrate the physiological roles of hypothalamic neurotransmitters and their potential as targets for the development of new drugs to treat obesity and other nutritional disorders. Neuropeptide Y (NPY) is expressed by neurones of the hypothalamic arcuate nucleus (ARC) that project to important appetite-regulating nuclei, including the paraventricular nucleus (PVN). NPY injected into the PVN is the most potent central appetite stimulant known, and also inhibits thermogenesis; repeated administration rapidly induces obesity. The ARC NPY neurones are stimulated by starvation, probably mediated by falls in circulating leptin and insulin (which both inhibit these neurones), and contribute to the increased hunger in this and other conditions of energy deficit. They therefore act homeostatically to correct negative energy balance. ARC NPY neurones also mediate hyperphagia and obesity in the ob/ob and db/db mice and fa/fa rat, in which leptin inhibition is lost through mutations affecting leptin or its receptor. -
Orexin Reverses Cholecystokinin-Induced Reduction in Feeding
ORIGINAL ARTICLE Orexin reverses cholecystokinin-induced reduction in feeding A. Asakawa,1 A. Inui,1 T. Inui,2 G. Katsuura,3 M. A. Fujino4 and M. Kasuga1 1Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan 2Inui Clinic, Osaka, Japan 3Shionogi Research Laboratories, Shionogi & Co Ltd, Shiga, Japan 4First Department of Internal Medicine, Yamanashi Medical University, Yamanashi, Japan Aim: This study was designed to investigate the effect of orexin on anorexia induced by cholecystokinin (CCK), a peripheral satiety signal. Methods: We administered orexin A (0.01±1 nmol/mouse) and CCK-8 (3 nmol/mouse) to mice. Food intake was measured at different time-points: 20 min, 1, 2 and 4 h post-intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) administrations. Results: Intracerebroventricular-administered orexin significantly increased food intake in a dose-dependent man- ner. The inhibitory effect of i.p.-administered CCK-8 on food intake was significantly negated by the simultaneous i.c.v. injection of orexin in a dose-dependent manner. Conclusions: Orexin reversed the CCK-induced loss of appetite. Our results indicate that orexin might be a promising target for pharmacological intervention in the treatment of anorexia and cachexia induced by various diseases. Keywords: orexin, cholecystokinin, mice, food intake, anorexia Received 28 March 2002; returned for revision 20 May 2002; revised version accepted 21 June 2002 Introduction However, the relationship between orexin and per- ipheral satiety systems still remains to be determined. Orexin is a hypothalamic neuropeptide identified as a We investigated the effect of orexin on anorexia induced ligand for an orphan G-protein coupled receptor [1±3]. -
Biocompatibility and Pharmacological Effects of Innovative Systems for Prolonged Drug Release Containing Dexketoprofen in Rats
polymers Article Biocompatibility and Pharmacological Effects of Innovative Systems for Prolonged Drug Release Containing Dexketoprofen in Rats Liliana Mititelu-Tartau 1,†, Maria Bogdan 2,* , Daniela Angelica Pricop 3,*, Beatrice Rozalina Buca 1,†, Loredana Hilitanu 1,†, Ana-Maria Pauna 1,†, Lorena Anda Dijmarescu 4,† and Eliza Gratiela Popa 5 1 Department of Pharmacology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; liliana.tartau@umfiasi.ro (L.M.-T.);beatrice-rozalina.buca@umfiasi.ro (B.R.B.); [email protected] (L.H.); ana-maria-raluca-d-pauna@umfiasi.ro (A.-M.P.) 2 Department of Pharmacology, Faculty of Pharmacy, University of Medicine and Pharmacy, 200349 Craiova, Romania 3 Department of Physics, Faculty of Physics, “Al. I. Cuza” University, 700506 Iasi, Romania 4 Department of Obstetrics-Gynecology, Faculty of Medicine, University of Medicine and Pharmacy, 200349 Craiova, Romania; [email protected] 5 Department of Pharmaceutical Technology, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; eliza.popa@umfiasi.ro * Correspondence: [email protected] (M.B.); [email protected] (D.A.P.) † These authors contributed equally to the study. Citation: Mititelu-Tartau, L.; Bogdan, Abstract: The present study reports on the in vivo biocompatibility investigation and evaluation of M.; Pricop, D.A.; Buca, B.R.; Hilitanu, the effects of liposomes containing dexketoprofen in somatic sensitivity in rats. Method: The lipo- L.; Pauna, A.-M.; Dijmarescu, L.A.; somes were prepared by entrapping dexketoprofen in vesicular systems stabilized with chitosan. The Popa, E.G. Biocompatibility and in vivo biocompatibility was evaluated after oral administration in white Wistar rats: Group I (DW): Pharmacological Effects of Innovative distilled water 0.3 mL/100 g body weight; Group II (DEX): dexketoprofen 10 mg/kg body weight Systems for Prolonged Drug Release (kbw); Group III (nano-DEX): liposomes containing dexketoprofen 10 mg/kbw. -
Neuropeptides Controlling Energy Balance: Orexins and Neuromedins
Neuropeptides Controlling Energy Balance: Orexins and Neuromedins Joshua P. Nixon, Catherine M. Kotz, Colleen M. Novak, Charles J. Billington, and Jennifer A. Teske Contents 1 Brain Orexins and Energy Balance ....................................................... 79 1.1 Orexin............................................................................... 79 2 Orexin and Feeding ....................................................................... 80 3 Orexin and Arousal ....................................................................... 83 J.P. Nixon • J.A. Teske Veterans Affairs Medical Center, Research Service (151), Minneapolis, MN, USA Department of Food Science and Nutrition, University of Minnesota, 1334 Eckles Avenue, St. Paul, MN 55108, USA Minnesota Obesity Center, University of Minnesota, 1334 Eckles Avenue, St. Paul, MN 55108, USA C.M. Kotz (*) Veterans Affairs Medical Center, GRECC (11 G), Minneapolis, MN, USA Veterans Affairs Medical Center, Research Service (151), Minneapolis, MN, USA Department of Food Science and Nutrition, University of Minnesota, 1334 Eckles Avenue, St. Paul, MN 55108, USA Minnesota Obesity Center, University of Minnesota, 1334 Eckles Avenue, St. Paul, MN 55108, USA e-mail: [email protected] C.M. Novak Department of Biological Sciences, Kent State University, Kent, OH, USA C.J. Billington Veterans Affairs Medical Center, Research Service (151), Minneapolis, MN, USA Veterans Affairs Medical Center, Endocrine Unit (111 G), Minneapolis, MN, USA Department of Food Science and Nutrition, University of Minnesota, 1334 Eckles Avenue, St. Paul, MN 55108, USA Minnesota Obesity Center, University of Minnesota, 1334 Eckles Avenue, St. Paul, MN 55108, USA H.-G. Joost (ed.), Appetite Control, Handbook of Experimental Pharmacology 209, 77 DOI 10.1007/978-3-642-24716-3_4, # Springer-Verlag Berlin Heidelberg 2012 78 J.P. Nixon et al. 4 Orexin Actions on Endocrine and Autonomic Systems ................................. 84 5 Orexin, Physical Activity, and Energy Expenditure .................................... -
Calcitonin Gene-Related Peptide Facilitates Sensitization of The
Zhang et al. The Journal of Headache and Pain (2020) 21:72 The Journal of Headache https://doi.org/10.1186/s10194-020-01145-y and Pain RESEARCH ARTICLE Open Access Calcitonin gene-related peptide facilitates sensitization of the vestibular nucleus in a rat model of chronic migraine Yun Zhang1, Yixin Zhang1*, Ke Tian2, Yunfeng Wang1, Xiaoping Fan1, Qi Pan1, Guangcheng Qin3, Dunke Zhang3, Lixue Chen2 and Jiying Zhou1 Abstract Background: Vestibular migraine has recently been recognized as a novel subtype of migraine. However, the mechanism that relate vestibular symptoms to migraine had not been well elucidated. Thus, the present study investigated vestibular dysfunction in a rat model of chronic migraine (CM), and to dissect potential mechanisms between migraine and vertigo. Methods: Rats subjected to recurrent intermittent administration of nitroglycerin (NTG) were used as the CM model. Migraine- and vestibular-related behaviors were analyzed. Immunofluorescent analyses and quantitative real- time polymerase chain reaction were employed to detect expressions of c-fos and calcitonin gene-related peptide (CGRP) in the trigeminal nucleus caudalis (TNC) and vestibular nucleus (VN). Morphological changes of vestibular afferent terminals was determined under transmission electron microscopy. FluoroGold (FG) and CTB-555 were selected as retrograde tracers and injected into the VN and TNC, respectively. Lentiviral vectors comprising CGRP short hairpin RNA (LV-CGRP) was injected into the trigeminal ganglion. Results: CM led to persistent thermal hyperalgesia, spontaneous facial pain, and prominent vestibular dysfunction, accompanied by the upregulation of c-fos labeling neurons and CGRP immunoreactivity in the TNC (c-fos: vehicle vs. CM = 2.9 ± 0.6 vs. -
Quercetin Attenuates Thermal Hyperalgesia and Cold Allodynia in STZ-Induced Diabetic Rats
Indian Journal of Experimental Biology Vol. 42, August 2004, pp. 766-769 Quercetin attenuates thermal hyperalgesia and cold allodynia in STZ-induced diabetic rats Muragundla Anjaneyulu & Kanwaljit Chopra* Pharmacology Division, Universit y In stitute of Pharmaceutical Sciences, Panjab University, Chandigarh , I 60 014, India Received 21 January 2004; revised 5 May 2004 Neuropathic pain is one of the important mi crovascular complications of diabetes. Oxidative stress and superoxide play a criti cal role in th e development of neurovascular complications in diabetes. Aim of th e present study was to eva lu ate the effec t of qu ercetin, a bi onavo noid on thermal nocicepti ve responses in streptozotoci n (STZ)-induced diabetic rats assessed by tail-immersion and hot plate meth ods. After 4-weeks of a single intra venous STZ injecti on (45 mg/kg body wei ght), diabetic rat s exhibited a significant th ermal hyperal gesia and cold all odynia along with in creased plasma glucose and decreased body weights as compared with control rat s. Chronic treatment with quercetin (I 0 mg/kg body wei ght; p.o) for 4- weeks starting from the 4' 11 week of STZ-injection significantly attenuated th e cold all odyni a as well as hypera lges ia. Results indicate th at qu ercetin, a natural anti ox idant, may be helpful in diabetic neuropathy. Keywords: Diabeti c neuropathy, Hyperalgesia, Quercetin, Cold all odyni a, Tail-immersion, Hot plate. Neuropathic pain is one of the most common Based on analgesic and antioxidant properties of complications in diabetes mellitus. -
Significance of the Orexinergic System in Modulating Stress-Related
Cohen et al. Translational Psychiatry (2020) 10:10 https://doi.org/10.1038/s41398-020-0698-9 Translational Psychiatry ARTICLE Open Access Significance of the orexinergic system in modulating stress-related responses in an animal model of post-traumatic stress disorder Shlomi Cohen1,2,MichaelA.Matar1, Ella Vainer1, Joseph Zohar3,4,ZeevKaplan1 and Hagit Cohen1,2 Abstract Converging evidence indicates that orexins (ORXs), the regulatory neuropeptides, are implicated in anxiety- and depression-related behaviors via the modulation of neuroendocrine, serotonergic, and noradrenergic systems. This study evaluated the role of the orexinergic system in stress-associated physiological responses in a controlled prospective animal model. The pattern and time course of activation of hypothalamic ORX neurons in response to predator-scent stress (PSS) were examined using c-Fos as a marker for neuronal activity. The relationship between the behavioral response pattern 7 days post-exposure and expressions of ORXs was evaluated. We also investigated the effects of intracerebroventricular microinfusion of ORX-A or almorexant (ORX-A/B receptor antagonist) on behavioral responses 7 days following PSS exposure. Hypothalamic levels of ORX-A, neuropeptide Y (NPY), and brain-derived neurotrophic factor (BDNF) were assessed. Compared with rats whose behaviors were extremely disrupted (post- traumatic stress disorder [PTSD]-phenotype), those whose behaviors were minimally selectively disrupted displayed significantly upregulated ORX-A and ORX-B levels in the hypothalamic nuclei. Intracerebroventricular microinfusion of ORX-A before PSS reduced the prevalence of the PTSD phenotype compared with that of artificial cerebrospinal fluid or almorexant, and rats treated with almorexant displayed a higher prevalence of the PTSD phenotype than did 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; untreated rats. -
Non-Commercial Use Only
Translational Medicine Reports 2019; volume 3:8142 Antibacterial and antiviral precursor, prepro-orexin, that is then potential of neuropeptides cleaved to generate the active molecules.10- Correspondence: Gianluigi Franci, 12 Orexin-A is a 33 amino acids peptide Department of Experimental Medicine, including 4 cysteines linked by two intra- University of Campania Luigi Vanvitelli, Carla Zannella, Debora Stelitano, chain disulfide bonds.13,14 Post-translational Via Costantinopoli 16, 80138 Naples, Italy. E-mail: [email protected] Veronica Folliero, Luciana Palomba, modifications of this peptide include a Tiziana Francesca Bovier, Roberta pyroglutamyl cyclization at the N-terminal Key words: Antibacterial; Antiviral; Astorri, Annalisa Chianese, and a C-terminal amidation. Orexin-B is a Neuropeptides; Orexins; Ghrelin. Marcellino Monda, Marilena Galdiero, 28 residue neuropeptide and like orexin-A Gianluigi Franci is characterized by a C-terminal amida- Contributions: CZ and DS contributed equal- 10,14 ly; VF, LP, TFB, RA, AC, MM, MG, data col- Department of Experimental Medicine, tion. The two neuropeptides share 46% 10 lecting and manuscript reviewing and refer- University of Campania Luigi Vanvitelli, of sequence homology. Two-dimensional NMR spectroscopy analysis of soluble ence search; GF, data collecting, figures Naples, Italy preparation and manuscript writing. orexin-B revealed that its structure consists 10 of two α–helices linked via a flexible loop. Conflict of interest: the authors declare no The lateral hypothalamus, where the neu- potential conflict of interest. Abstract ropeptides are generated, is responsible for eating behavior and energy homeosta- Funding: VALEREplus Program. The emergence of multidrug resistant sis.6,15,16 Indeed, orexins play a key role in bacteria is a global health threat and the dis- feeding behavior and body weight regula- Received for publication: 28 February 2019. -
Effect of Restraint Stress on Nociceptive Responses in Rats: Role of the Histaminergic System
Niger. J. Physiol. Sci. 26(December 2011) 139 – 141 www.njps.com.ng Short communication Effect of restraint stress on nociceptive responses in rats: role of the histaminergic system *Ibironke G F and Mordi N E Department of Physiology, College of Medicine, University of Ibadan,Ibadan, Nigeria. Summary: Stress induced analgesia (SIA) is well known, but the reverse phenomenon, hyperalgesia is poorly documented. This study investigated the role of the histaminergic system in restraint stress hyperalgesia in rats, using thermal stimulation method (hot plate and tail flick tests). Paw licking and tail withdrawal latencies were taken before and after restraint for about one hour. Significant decreases (p< 0.05) were obtained in these latencies after the restraint in both tests. Administration of H1 and H2 receptor blockers, chlorpheniramine and cimetidine respectively 30 mins before the restraint still resulted in significant (p<0.05) reductions in these latencies, connoting the persistence of hyperalgesia, showing that histamine H1 and H2 receptors did not participate in the mechanism of restraint stress hyperalgesia. We therefore suggest a histaminergic independent mechanism for restraint stress induced hyperalgesia. Keywords: Restraint stress, Thermal stimulation, Hyperalgesia, Histamine. ©Physiological Society of Nigeria *Address for correspondence: [email protected] Manuscript Accepted: July, 2011 INTRODUCTION higher levels of suffering during stressful episodes (Conrad et al, 2007, Fishbain et al, 2006). Numerous Stress can have bilateral effects on pain related pre-clinical models have been developed to reproduce phenomena. Firstly, acute stress can produce various pain modalities that are encountered in the analgesia in humans and animals (Amit and Galina, clinic, however, animal studies assessing the 1986). -
Differential Control of Opioid Antinociception to Thermal Stimuli in a Knock-In Mouse Expressing Regulator of ␣ G-Protein Signaling-Insensitive G O Protein
The Journal of Neuroscience, March 6, 2013 • 33(10):4369–4377 • 4369 Cellular/Molecular Differential Control of Opioid Antinociception to Thermal Stimuli in a Knock-In Mouse Expressing Regulator of ␣ G-Protein Signaling-Insensitive G o Protein Jennifer T. Lamberts,1 Chelsea E. Smith,1 Ming-Hua Li,3 Susan L. Ingram,3 Richard R. Neubig,1,2 and John R. Traynor1 1Department of Pharmacology, and 2Center for the Discovery of New Medicines, University of Michigan Medical School, Ann Arbor, Michigan 48109, and 3Department of Neurological Surgery, Oregon Health and Science University, Portland, Oregon 97239 Regulator of G-protein signaling (RGS) proteins classically function as negative modulators of G-protein-coupled receptor signaling. In vitro, RGS proteins have been shown to inhibit signaling by agonists at the -opioid receptor, including morphine. The goal of the present study was to evaluate the contribution of endogenous RGS proteins to the antinociceptive effects of morphine and other opioid agonists. ␣ ␣ G184S ␣ To do this, a knock-in mouse that expresses an RGS-insensitive (RGSi) mutant G o protein, G o (G o RGSi), was evaluated for ␣ morphine or methadone antinociception in response to noxious thermal stimuli. Mice expressing G o RGSi subunits exhibited a naltrexone-sensitive enhancement of baseline latency in both the hot-plate and warm-water tail-withdrawal tests. In the hot-plate test, a measureofsupraspinalnociception,morphineantinociceptionwasincreased,andthiswasassociatedwithanincreasedabilityofopioids to inhibit presynaptic GABA neurotransmission in the periaqueductal gray. In contrast, antinociception produced by either morphine or methadone was reduced in the tail-withdrawal test, a measure of spinal nociception. In whole-brain and spinal cord homogenates from ␣ ␣ mice expressing G o RGSi subunits, there was a small loss of G o expression and an accompanying decrease in basal G-protein activity. -
List of Entries
List of Entries Essays are shown in bold A Afferent Fibers (Neurons) Acid-Sensing Ion Channels AFibers(A-Fibers) NICOLAS VOILLEY,MICHEL LAZDUNSKI A Beta(β) Afferent Fibers Acinar Cell Injury A Delta(δ) Afferent Fibers (Axons) Acrylamide A Delta(δ)-Mechanoheat Receptor Acting-Out A Delta(δ)-Mechanoreceptor Action AAV Action Potential Abacterial Meningitis Action Potential Conduction of C-Fibres Abdominal Skin Reflex Action Potential in Different Nociceptor Populations Abduction Actiq® Aberrant Drug-Related Behaviors ® Ablation Activa Abnormal Illness Affirming States Activation Threshold Abnormal Illness Behavior Activation/Reassurance GEOFFREY HARDING Abnormal Illness Behaviour of the Unconsciously Motivated, Somatically Focussed Type Active Abnormal Temporal Summation Active Inhibition Abnormal Ureteric Peristalsis in Stone Rats Active Locus Abscess Active Myofascial Trigger Point Absolute Detection Threshold Activities of Daily Living Absorption Activity ACC Activity Limitations Accelerated Recovery Programs Activity Measurement Acceleration-Deceleration Injury Activity Mobilization Accelerometer Activity-Dependent Plasticity Accommodation (of a Nerve Fiber) Acupuncture Acculturation Acupuncture Efficacy EDZARD ERNST Accuracy and Reliability of Memory Acupuncture Mechanisms β ACE-Inhibitors, Beta( )-Blockers CHRISTER P.O. C ARLSSON Acetaminophen Acupuncture-Like TENS Acetylation Acute Backache Acetylcholine Acute Experimental Monoarthritis Acetylcholine Receptors Acute Experimental -
Identification of Orexin A-And Orexin Type 2 Receptor-Positive Cells in the Gastrointestinal Tract of Neonatal Dogs
ORIGINAL PAPER Identification of orexin A- and orexin type 2 receptor-positive cells in the gastrointestinal tract of neonatal dogs C. Dall’Aglio,1 L. Pascucci,1 F. Mercati,1 A. Giontella,2 V. Pedini,1 P. Scocco,3 P. Ceccarelli1 1Dipartimento di Scienze Biopatologiche Veterinarie ed Igiene delle Produzioni Animali ed Alimentari, Sezione di Anatomia Veterinaria; 2Dip. di Patologia, Diagnostica e Clinica Veterinaria, Sez. di Scienze Sperimentali e Biotecnologie Applicate, Facoltà di Medicina Veterinaria, Perugia; 3Dipartimento di Scienze Ambientali, Facoltà di Medicina Veterinaria, Matelica, Italy t has been known for some time that the ©2008 European Journal of Histochemistry endocrine cells distributed in the gastrointesti- The presence and distribution of cells positive to orexin A Inal mucosa, together with those present in the (OXA) and to orexin type 2 receptor (OX2R) were investigat- pancreas, form the gastroenteropancreatic ed in the gastrointestinal tract of neonatal dogs by means of immunohistochemical techniques. The orexin A-positive cells endocrine system (Calingasan et al., 1984). From were identified with some of the endocrine cells in the stom- the first studies describing, by histochemical tech- ach and in the duodenum; they were both of the open and niques, the presence of numerous granules in the closed type and were lacking in the large intestine. In the stomach, a large subset of orexin A-positive cells also basal cytoplasmic portion of the endocrine cells showed gastrin-like immunoreactivity while, in the duode- scattered among epithelial gut cells (Singh, 1964) , num, many of them seemed to store serotonin. The orexin many steps forward have been made thanks to more type 2 receptor-positive cells were evidenced all along the and more sophisticated histochemical and immuno- gastrointestinal tract examined, also in the large intestine, and they showed the same morphological characteristics as histochemical procedures and to the commercial those positive to orexin A.