DOCSLIB.ORG

Recent Advances in Pain Management

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Recent Advances in Pain Management International Journal of Basic & Clinical Pharmacology Ba skaran P et al. Int J Basic Clin Pharmacol. 2021 Jan;10(1):133-139 http:// www.ijbcp.com pISSN 2319-2003 | eISSN 2279-0780 DOI: https://dx.doi.org/10.18203/2319-2003.ijbcp20205553 Review Article Recent advances in pain management Priyadarsini Baskaran1, Venkatraman Karthikeayan2, Anusha Natarajan3* 1Medical Monitor, Clinirx CRO, Chennai, Tamil Nadu, India 2Consultant Neuro-Immunologist, Global Hospitals, Chennai , Tamil Nadu, India 3Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India Received: 26 May 2020 Revised: 01 December 2020 Accepted: 12 December 2020 *Correspondence: Dr. Anusha Natarajan, Email: [email protected] Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Pain is one of the most common complaints for which patients approach physicians. In spite of this there is a huge unmet need for developing medications for pain that are safe and efficacious. Owing to the heterogeneity of clinical pain and complex pathophysiology, target identification for drug development is difficult. Preclinical models have also proven unreliable for the development of novel analgesics. Recent advances in understanding the physiology of nociception has enabled the development of novel analgesics including abuse deterrent opioids, drugs targeting several receptors, ion channels and enzymes. This review will attempt to cover the physiology of nociception focusing on the novel targets, the challenges in development of novel analgesics and give an overview of the recently developed drugs and those in the pipeline for the management of pain. Keywords: Nociception, Pain therapy, Recent Advances in pain therapy INTRODUCTION Pain (including widespread pain syndromes) can be due to inflammation or tissue damage, cancer, or lesions of the The International Association for the Study of Pain defines nervous system leading to spontaneous pain, hyperalgesia pain as “an unpleasant sensory and emotional experience and allodynia. The available drugs like non-steroidal anti- associated with actual or potential tissue damage or inflammatory drugs (NSAIDS) and opioids with good described in terms of such damage.” Pain is the most analgesic efficacy are coupled with deleterious side common neurological complaint. Pain can be broadly effects. The adjuvant drugs used like amine reuptake classified as acute and chronic pain. Acute pain is usually inhibitors and anti-epileptics have poor analgesic efficacy a symptom of the underlying disease condition and has a with side effects that decrease the quality of life. protective role biologically while chronic pain lacks a biological protective role and is a disease condition in There is an unmet need for the development of novel itself, presenting with symptoms of refractory pain, effective and safe analgesics without abuse liability. functional and psychological impairment, and disability.1 An annual cost of 560–635 billion dollars is spent in direct PHYSIOLOGY OF NOCICEPTION treatment costs and lost productivity due to chronic pain causing a huge economic burden to the community.2 The physiological process by which pain is perceived is known as nociception. Nociceptors have unmyelinated (C- International Journal of Basic & Clinical Pharmacology | January 2021 | Vol 10 | Issue 1 Page 133 Baskaran P et al. Int J Basic Clin Pharmacol. 2021 Jan;10(1):133-139 fibre) or thinly myelinated (Aδ-fibre) axons. Stimulation ganglia of the spinal cord or in the trigeminal ganglia. The of afferent Aδ nociceptive fibres causes a sharp, well- nociceptors express ion-channel receptors (belonging to localized pain sensation. Activation of nociceptive C fibres the transient receptor potential (TRP) family of ion is associated with a dull, burning or aching, and poorly channel receptors) which convert the noxious stimuli into localized pain. Their cell bodies lie in the dorsal root action potentials. Figure 1: Modulation of nociceptive pathways.3 These ion channels are mostly voltage gated sodium projections that descend from the brainstem to the dorsal channels. Action potentials that result from the horn. The major inhibitory neurotransmitters in the dorsal transduction of noxious stimuli are conducted along the horn of the spinal cord are opioid peptides, norepinephrine, axon of the sensory neuron into the spinal cord where they serotonin (5-HT), glycine, and GABA. At the level of the synapse on the dorsal horn. Glutamate is released at this spinal cord, cells located in the dorsal horn modulate the synapse. The release of neurotransmitters is modulated by sensation of pain. Activation of non-nociceptive afferent N-type voltage gated calcium channels. The dorsal horn fibres may suppress the nociceptive transmission in the neurons send projections to supra-spinal areas in the spinal cord. This is the basis of “the gate control theory of brainstem, hypothalamus, and thalamus and then, through pain”. Descending inhibitory pathways from the brain relay neurons, to the cortex where the sensation of pain is further modulate pain transmission. The inhibitory perceived. Glutamate and substance P are the major pathways include opioid, noradrenergic and serotonergic transmitters involved in pain transmission. systems. CENTRAL MODULATION OF PAIN2 CHRONIC PAIN2 Synaptic transmission in the spinal cord is regulated by the On repeated painful stimuli to the nociceptors, the actions of both local inhibitory interneurons and threshold for their activation is decreased. This is called International Journal of Basic & Clinical Pharmacology | January 2021 | Vol 10 | Issue 1 Page 134 Baskaran P et al. Int J Basic Clin Pharmacol. 2021 Jan;10(1):133-139 auto-sensitisation. As the painful stimulus continues there of pain with even minor/ no stimulus. This property of the is increased membrane excitability. Finally gene alteration neurons to change is called neuronal plasticity. takes place leading to prolonged and increased perception Figure 2: Newer targets being explored for development of analgesics.4 DRUGS ACTING ON OPIOID RECEPTOR LIKE CB2 receptors showed promise as analgesics in preclinical RECEPTOR-1 (ORL-1) trials. Olorinab, a highly potent CB2 agonist has completed phase 2a trials for treatment of visceral pain. ORL-1 is also known as nociception receptor. It is Tedalinab, another potent and highly selective CB2 expressed in the central nervous system (CNS). On agonist has also shown analgesic and anti-inflammatory activation by its ligand nociceptin, it causes closure of effects in phase 1 trials. Other molecules like LY2828360, voltage gated calcium channels and opening of potassium S-777469, KHK6188 were discontinued for lack of channels reducing excitability.5 Cebranopadol is a low efficacy in clinical trials. selectivity ORL-1 agonist and was found to be as effective as tapentadol and superior to placebo in phase 2 trials. Angiotensin type 2 receptor (AT2R) inhibitors Buprenorphine also has ORL-1 agonist activity.6 The AT2 receptors are expressed in the sensory neurons of HISTAMINE RECEPTORS humans and have been implicated in the development of neuropathic pain. AT2R inhibitors are being developed for The H3 receptor subtype (H3R) is an inhibitory the treatment of neuropathic pain. The molecule EMA-401 autoreceptor located on both pre and postsynaptic neurons. is now in phase 2b of clinical development. It is being Activation of H3Rs in the skin reduces calcitonin gene- investigated for the treatment of painful diabetic related peptide (CGRP) and substance P release, leading to neuropathy (EMPADINE trial) and post herpetic neuralgia 7,8 an anti-inflammatory response. The compound (EMPHENE trial). GSK189254 (H3 agonists) was found effective in animal models of neuropathic pain.5 Alpha (α2) adrenergic receptors agonists DRUGS TARGETING G-PROTEIN COUPLED α2 adrenergic receptors inhibit the presynaptic release of RECEPTORS neuropeptides in the spinal cord and bring about reduction in pain. Phase 2 trials of an inhaled formulation of The receptor systems involved in pain pathways include dexmedetomidine showed efficacy in reducing cannabinoid receptors, angiotensin type 2 receptors and α2 postoperative pain but was accompanied by adverse 5 adrenergic receptors. effects like hypotension and bradycardia. Cannabinoid receptors agonists7 Chemokine receptors The CB1 and CB2 receptors have been investigated as Chemokines activate and sensitize the sodium channels potential targets for management of pain. CB1 receptors and TRPV1 receptors. They help in maintenance of pain. have severe psychomimetic effects and abuse potential but They’re also implicated in the causation of opioid International Journal of Basic & Clinical Pharmacology | January 2021 | Vol 10 | Issue 1 Page 135 Baskaran P et al. Int J Basic Clin Pharmacol. 2021 Jan;10(1):133-139 tolerance and opioid induced hyperalgesia. CCR2 receptor Calcium channels antagonist AZD242 was developed and showed promise in preclinical rodent models but did not show any analgesic Voltage dependent calcium channels regulate cellular efficacy in human studies.5 excitability and mediate release of synaptic vesicles. The commonly used therapeutic agents gabapentin and DRUGS TARGETING ION CHANNELS
Load more

Recommended publications
  • PRODUCT INFORMATION ABT-594 Item No
    PRODUCT INFORMATION ABT-594 Item No. 22822 CAS Registry No.: 203564-54-9 Formal Name: 5-[(2R)-2-azetidinylmethoxy]-2- H chloro-pyridine, monohydrochloride N Synonyms: Ebanicline, Tebanicline O MF: C9H11ClN2O • HCl FW: 235.1 N Purity: ≥95% Cl Supplied as: A solid • HCl Storage: -20°C Stability: ≥2 years Information represents the product specifications. Batch specific analytical results are provided on each certificate of analysis. Laboratory Procedures ABT-594 is supplied as a solid. A stock solution may be made by dissolving the ABT-594 in the solvent of choice. ABT-594 is soluble in the organic solvent DMSO, which should be purged with an inert gas. Description ABT-594 is a potent agonist of neuronal α4β2 subunit-containing nicotinic acetylcholine receptors 1 (nAChRs; Ki = 37 pM in a radioligand binding assay). It is selective for neuronal nAChRs over neuromuscular α1β1δγ subunit-containing nAChRs (Ki = 10,000 nM), α1B-, α2B-, and α2C-adrenergic receptors (Kis = 890, 597, and 342 nM, respectively), and 70 other receptors, enzymes, and transporters 86 + (Kis = >1,000 nM) in radioligand binding assays. ABT-594 induces [ Rb ] efflux in K177 cells transfected with human neuronal α4β2 subunit-containing nAChRs (EC50 = 140 nM). In vivo, ABT-594 (0.05 and 0.01 mg/kg, s.c.) increases latency to paw withdrawal in a hot-plate test in rats.2 It also induces hypothermia, seizures, and an increase in blood pressure. References 1. Donnelly-Roberts, D.L., Puttfarcken, P.S., Kuntzweiler, T.A., et al. ABT-594 [(R)-5-(2-azetidinylmethoxy)- 2-chloropyridine]: A novel, orally effective analgesic acting via neuronal nicotinic acetylcholine receptors: I.
    [Show full text]
  • Could Mycolactone Inspire New Potent Analgesics? Perspectives and Pitfalls
    toxins Review Could Mycolactone Inspire New Potent Analgesics? Perspectives and Pitfalls 1 2 3, 4, , Marie-Line Reynaert , Denis Dupoiron , Edouard Yeramian y, Laurent Marsollier * y and 1, , Priscille Brodin * y 1 France Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204-CIIL-Center for Infection and Immunity of Lille, F-59000 Lille, France 2 Institut de Cancérologie de l’Ouest Paul Papin, 15 rue André Boquel-49055 Angers, France 3 Unité de Microbiologie Structurale, Institut Pasteur, CNRS, Univ. Paris, F-75015 Paris, France 4 Equipe ATIP AVENIR, CRCINA, INSERM, Univ. Nantes, Univ. Angers, 4 rue Larrey, F-49933 Angers, France * Correspondence: [email protected] (L.M.); [email protected] (P.B.) These three authors contribute equally to this work. y Received: 29 June 2019; Accepted: 3 September 2019; Published: 4 September 2019 Abstract: Pain currently represents the most common symptom for which medical attention is sought by patients. The available treatments have limited effectiveness and significant side-effects. In addition, most often, the duration of analgesia is short. Today, the handling of pain remains a major challenge. One promising alternative for the discovery of novel potent analgesics is to take inspiration from Mother Nature; in this context, the detailed investigation of the intriguing analgesia implemented in Buruli ulcer, an infectious disease caused by the bacterium Mycobacterium ulcerans and characterized by painless ulcerative lesions, seems particularly promising. More precisely, in this disease, the painless skin ulcers are caused by mycolactone, a polyketide lactone exotoxin. In fact, mycolactone exerts a wide range of effects on the host, besides being responsible for analgesia, as it has been shown notably to modulate the immune response or to provoke apoptosis.
    [Show full text]
  • Summary Analgesics Dec2019
    Status as of December 31, 2019 UPDATE STATUS: N = New, A = Advanced, C = Changed, S = Same (No Change), D = Discontinued Update Emerging treatments for acute and chronic pain Development Status, Route, Contact information Status Agent Description / Mechanism of Opioid Function / Target Indication / Other Comments Sponsor / Originator Status Route URL Action (Y/No) 2019 UPDATES / CONTINUING PRODUCTS FROM 2018 Small molecule, inhibition of 1% diacerein TWi Biotechnology / caspase-1, block activation of 1 (AC-203 / caspase-1 inhibitor Inherited Epidermolysis Bullosa Castle Creek Phase 2 No Topical www.twibiotech.com NLRP3 inflamasomes; reduced CCP-020) Pharmaceuticals IL-1beta and IL-18 Small molecule; topical NSAID Frontier 2 AB001 NSAID formulation (nondisclosed active Chronic low back pain Phase 2 No Topical www.frontierbiotech.com/en/products/1.html Biotechnologies ingredient) Small molecule; oral uricosuric / anti-inflammatory agent + febuxostat (xanthine oxidase Gout in patients taking urate- Uricosuric + 3 AC-201 CR inhibitor); inhibition of NLRP3 lowering therapy; Gout; TWi Biotechnology Phase 2 No Oral www.twibiotech.com/rAndD_11 xanthine oxidase inflammasome assembly, reduced Epidermolysis Bullosa Simplex (EBS) production of caspase-1 and cytokine IL-1Beta www.arraybiopharma.com/our-science/our-pipeline AK-1830 Small molecule; tropomyosin Array BioPharma / 4 TrkA Pain, inflammation Phase 1 No Oral www.asahi- A (ARRY-954) receptor kinase A (TrkA) inhibitor Asahi Kasei Pharma kasei.co.jp/asahi/en/news/2016/e160401_2.html www.neurosmedical.com/clinical-research;
    [Show full text]
  • (19) United States (12) Patent Application Publication (10) Pub
    US 20130289061A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0289061 A1 Bhide et al. (43) Pub. Date: Oct. 31, 2013 (54) METHODS AND COMPOSITIONS TO Publication Classi?cation PREVENT ADDICTION (51) Int. Cl. (71) Applicant: The General Hospital Corporation, A61K 31/485 (2006-01) Boston’ MA (Us) A61K 31/4458 (2006.01) (52) U.S. Cl. (72) Inventors: Pradeep G. Bhide; Peabody, MA (US); CPC """"" " A61K31/485 (201301); ‘4161223011? Jmm‘“ Zhu’ Ansm’ MA. (Us); USPC ......... .. 514/282; 514/317; 514/654; 514/618; Thomas J. Spencer; Carhsle; MA (US); 514/279 Joseph Biederman; Brookline; MA (Us) (57) ABSTRACT Disclosed herein is a method of reducing or preventing the development of aversion to a CNS stimulant in a subject (21) App1_ NO_; 13/924,815 comprising; administering a therapeutic amount of the neu rological stimulant and administering an antagonist of the kappa opioid receptor; to thereby reduce or prevent the devel - . opment of aversion to the CNS stimulant in the subject. Also (22) Flled' Jun‘ 24’ 2013 disclosed is a method of reducing or preventing the develop ment of addiction to a CNS stimulant in a subj ect; comprising; _ _ administering the CNS stimulant and administering a mu Related U‘s‘ Apphcatlon Data opioid receptor antagonist to thereby reduce or prevent the (63) Continuation of application NO 13/389,959, ?led on development of addiction to the CNS stimulant in the subject. Apt 27’ 2012’ ?led as application NO_ PCT/US2010/ Also disclosed are pharmaceutical compositions comprising 045486 on Aug' 13 2010' a central nervous system stimulant and an opioid receptor ’ antagonist.
    [Show full text]
  • Ketamine: an Update for Its Use in Complex Regional Pain Syndrome
    xperim & E en l ta a l ic P in h Bentley et al., Clin Exp Pharmacol 2015, 5:2 l a C r m f Journal of DOI: 10.4172/2161-1459.1000169 o a l c a o n l o r g u y o J ISSN: 2161-1459 Clinical and Experimental Pharmacology Commentry Open Access Ketamine: An Update for Its Use in Complex Regional Pain Syndrome and Major Depressive Disorder William E Bentley*, Michael Sabia, Michael E Goldberg and Irving W Wainer Cooper University Hospital, Camden, New Jersey, United States of America Abstract In recent years, there has been significant research in regard to the efficacy of ketamine in regards to treating Complex Regional Pain Syndrome (CRPS) and Major Depressive Disorder (MDD). Many patients have had substantial symptomatic relief; however, not all patients have had positive results. This has prompted current research with evidence to suggest certain biomarkers exist that would infer which patients will/will not respond to ketamine treatment. Current biomarkers of interest include D-Serine (D-Ser) and magnesium, which will be discussed. Whether or not D-Ser and/or magnesium levels should be checked and possibly dictate therapy is an area of future research. It is also possible that downstream metabolites of ketamine are the key to successful therapy. Keywords: Complex regional pain syndrome; Major Depressive thoughts; and slowing of speech and action. These changes must last a Disorder(MDD); Ketamine minimum of 2 weeks and interfere considerably with work and family relations” [6]. Treatment options include antidepressant medications, Complex Regional Pain Syndrome (CRPS) and Major Depressive cognitive behavioral therapy, and interpersonal therapy.
    [Show full text]
  • Emerging Pharmacological Strategies for the Treatment
    Emerging pharmacological strategies for the treatment of fibromyalgia LAWSON, Kim Available from Sheffield Hallam University Research Archive (SHURA) at: http://shura.shu.ac.uk/15300/ This document is the author deposited version. You are advised to consult the publisher's version if you wish to cite from it. Published version LAWSON, Kim (2017). Emerging pharmacological strategies for the treatment of fibromyalgia. World Journal of Pharmacology, 6 (1), 1-10. Repository use policy Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Users may download and/or print one copy of any article(s) in SHURA to facilitate their private study or for non- commercial research. You may not engage in further distribution of the material or use it for any profit-making activities or any commercial gain. Sheffield Hallam University Research Archive http://shura.shu.ac.uk World Journal of WJ P Pharmacology Submit a Manuscript: http://www.wjgnet.com/esps/ World J Pharmacol 207 March 9; 6(): -0 DOI: 0.5497/wjp.v6.i. ISSN 2220-392 (online) MINIREVIEWS Emerging pharmacological strategies for the treatment of ibromyalgia Kim Lawson Kim Lawson, Department of Biosciences and Chemistry, Bio­ presenting with a complex of symptoms dominated by molecular Sciences Research Centre, Shefield Hallam University, chronic widespread pain associated with the existence of a Faculty of Health and Wellbeing, Sheffield S1 1WB, United range of co-morbidities, such as fatigue, sleep disturbance, Kingdom cognitive impairment, anxiety and depression. Current treatments include drugs that target serotonin and nor- Author contributions: Lawson K researched the materials for the article and wrote the manuscript.
    [Show full text]
  • Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011
    CLASSIFICATION DECISIONS TAKEN BY THE HARMONIZED SYSTEM COMMITTEE FROM THE 47TH TO 60TH SESSIONS (2011 - 2018) WORLD CUSTOMS ORGANIZATION Rue du Marché 30 B-1210 Brussels Belgium November 2011 Copyright © 2011 World Customs Organization. All rights reserved. Requests and inquiries concerning translation, reproduction and adaptation rights should be addressed to [email protected]. D/2011/0448/25 The following list contains the classification decisions (other than those subject to a reservation) taken by the Harmonized System Committee ( 47th Session – March 2011) on specific products, together with their related Harmonized System code numbers and, in certain cases, the classification rationale. Advice Parties seeking to import or export merchandise covered by a decision are advised to verify the implementation of the decision by the importing or exporting country, as the case may be. HS codes Classification No Product description Classification considered rationale 1. Preparation, in the form of a powder, consisting of 92 % sugar, 6 % 2106.90 GRIs 1 and 6 black currant powder, anticaking agent, citric acid and black currant flavouring, put up for retail sale in 32-gram sachets, intended to be consumed as a beverage after mixing with hot water. 2. Vanutide cridificar (INN List 100). 3002.20 3. Certain INN products. Chapters 28, 29 (See “INN List 101” at the end of this publication.) and 30 4. Certain INN products. Chapters 13, 29 (See “INN List 102” at the end of this publication.) and 30 5. Certain INN products. Chapters 28, 29, (See “INN List 103” at the end of this publication.) 30, 35 and 39 6. Re-classification of INN products.
    [Show full text]
  • Efforts Towards the Synthesis of Epibatidine By: Marianne Hanna
    Efforts Towards the Synthesis of Epibatidine By: Marianne Hanna (Junior-Biochemistry major) Faculty Advisor: Dr. Thomas Montgomery Duquesne University- Bayer School of Natural Sciences 1 Abstract: Epibatidine is a naturally toxic chemical found in the secretion of poison dart frogs. Given its structural similarities to the compound nicotine epibatidine binds strongly to nicotine receptors in the central nervous system (CTS). Epibatidine’s bioactivity arises from its unique geometry which allows it to bind to the α4β2 subunit in the nicotinic receptor. This triggers an analgesic effect without a release of dopamine, differentiating its activity from opioids. Prior efforts towards synthesizing epibatidine and its analogs have involved many steps making them untenable for pharmaceutical use. By using computational and experimental methods to study the mechanism for an interrupted Polonovski [3+2] cycloaddition which will give direct access to the epibatidine core motif. By synthesizing strategic derivatives of epibatidine through this route we will investigate opioid alternatives which lack many of their addictive qualities. Background: Epibatidine is a toxic alkaloid that is isolated from the skin of poison dart tree frog Epipedobates tricolor, secretions from the frog are used by indigenous tribes in darts for hunting.1 The chemical structure was established in 1992 using NMR spectroscopy (proton NMR).2 Epibatidine possesses significant medicinal properties, it functions as an analgesic agent by binding to the nicotinic acetylcholine receptors (nAChRs) instead of the opioid receptors.3 Moreover it displays an affinity for said receptors that is 100- to 200-fold higher than nicotine. The alkaloid interacts with Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels and are expressed central and peripherally.
    [Show full text]
  • ACPA Guide to Pain Management
    [Document title] [Document subtitle] Abstract [Draw your reader in with an engaging abstract. It is typically a short summary of the document. When you’re ready to add your content, just click here and start typing.] ACPA [Email address] 1 ACPA Resource Guide To Chronic Pain Management An Integrated Guide to Medical, Interventional, Behavioral, Pharmacologic and Rehabilitation Therapies 2019 Edition American Chronic Pain Association P.O. Box 850 Rocklin, CA 95677 Tel 800-533-3231 Fax 916-652-8190 E-mail [email protected] Web Site http://www.theacpa.org Copyright 2019 American Chronic Pain Association, Inc. All rights reserved. No portion of this book may be reproduced without permission of the American Chronic Pain Association, Inc. 2 Table of Contents A STATEMENT FROM THE ACPA BOARD OF DIRECTORS ...........................................................................................................................5 INTRODUCTION ........................................................................................................................................................................................................6 OVERVIEW OF CHRONIC PAIN TREATMENT ..................................................................................................................................................8 WHAT DOES SUCCESSFUL PAIN TREATMENT LOOK LIKE? .......................................................................................................................8 PAIN TYPES, SOURCES & CLASSIFICATION .....................................................................................................................................................9
    [Show full text]
  • Membrane Stabilizer Medications in the Treatment of Chronic Neuropathic Pain: a Comprehensive Review
    Current Pain and Headache Reports (2019) 23: 37 https://doi.org/10.1007/s11916-019-0774-0 OTHER PAIN (A KAYE AND N VADIVELU, SECTION EDITORS) Membrane Stabilizer Medications in the Treatment of Chronic Neuropathic Pain: a Comprehensive Review Omar Viswanath1,2,3 & Ivan Urits4 & Mark R. Jones4 & Jacqueline M. Peck5 & Justin Kochanski6 & Morgan Hasegawa6 & Best Anyama7 & Alan D. Kaye7 Published online: 1 May 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Purpose of Review Neuropathic pain is often debilitating, severely limiting the daily lives of patients who are affected. Typically, neuropathic pain is difficult to manage and, as a result, leads to progression into a chronic condition that is, in many instances, refractory to medical management. Recent Findings Gabapentinoids, belonging to the calcium channel blocking class of drugs, have shown good efficacy in the management of chronic pain and are thus commonly utilized as first-line therapy. Various sodium channel blocking drugs, belonging to the categories of anticonvulsants and local anesthetics, have demonstrated varying degrees of efficacy in the in the treatment of neurogenic pain. Summary Though there is limited medical literature as to efficacy of any one drug, individualized multimodal therapy can provide significant analgesia to patients with chronic neuropathic pain. Keywords Neuropathic pain . Chronic pain . Ion Channel blockers . Anticonvulsants . Membrane stabilizers Introduction Neuropathic pain, which is a result of nervous system injury or lives of patients who are affected. Frequently, it is difficult to dysfunction, is often debilitating, severely limiting the daily manage and as a result leads to the progression of a chronic condition that is, in many instances, refractory to medical This article is part of the Topical Collection on Other Pain management.
    [Show full text]
  • JPET #226803 Title Page Effects of Nicotinic Acetylcholine Receptor
    JPET Fast Forward. Published on September 10, 2015 as DOI: 10.1124/jpet.115.226803 This article has not been copyedited and formatted. The final version may differ from this version. 1 JPET #226803 Title Page Effects of nicotinic acetylcholine receptor agonists in assays of acute pain-stimulated and pain- depressed behaviors in rats Kelen. C. Freitas, F. Ivy Carroll, and S. Stevens Negus Downloaded from Department of Pharmacology and Toxicology, Virginia Commonwealth University, jpet.aspetjournals.org Richmond VA, USA Research Triangle Institute, Research Triangle Park, NC, USA at ASPET Journals on September 26, 2021 JPET Fast Forward. Published on September 10, 2015 as DOI: 10.1124/jpet.115.226803 This article has not been copyedited and formatted. The final version may differ from this version. 2 JPET #226803 Running Title Page Effects of nicotinic drugs on pain-depressed behavior Address correspondence to: Kelen Freitas, Department of Pharmacology and Toxicology, Downloaded from Virginia Commonwealth University, 410 North 12th Street, PO Box 980613, Richmond, VA 23298. Telephone: (804) 828-3158 Fax: (804) 828-2117 Email: [email protected] jpet.aspetjournals.org Number of text pages: 37 at ASPET Journals on September 26, 2021 Number of tables: 1 Number of figures: 6 Number of references: 76 Number of words in the abstract: 241 Number of words in the introduction: 746 Number of words in the discussion: 1.250 List of non-standard abbreviations nAChRs, nicotinic acetylcholine receptors DhβE, dihydro-ß-ertyroidine MD-354, Meta-chlorophenylguanidine Nicotine, (-)-nicotine hydrogen tartrate PNU 282987, N-(3R)-1-Azabicyclo[2.2.2]oct-3-yl-4-chlorobenzamide 5-I-A-85380, 5-[123I]iodo-3-[2(S)-2-azetidinylmethoxy]pyridine ICSS, intracranial self-stimulation MCR, maximum control rate %MCR, percentage of MCR ANOVA, analysis of variance JPET Fast Forward.
    [Show full text]
  • Modifications to the Harmonized Tariff Schedule of the United States To
    U.S. International Trade Commission COMMISSIONERS Shara L. Aranoff, Chairman Daniel R. Pearson, Vice Chairman Deanna Tanner Okun Charlotte R. Lane Irving A. Williamson Dean A. Pinkert Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Modifications to the Harmonized Tariff Schedule of the United States to Implement the Dominican Republic- Central America-United States Free Trade Agreement With Respect to Costa Rica Publication 4038 December 2008 (This page is intentionally blank) Pursuant to the letter of request from the United States Trade Representative of December 18, 2008, set forth in the Appendix hereto, and pursuant to section 1207(a) of the Omnibus Trade and Competitiveness Act, the Commission is publishing the following modifications to the Harmonized Tariff Schedule of the United States (HTS) to implement the Dominican Republic- Central America-United States Free Trade Agreement, as approved in the Dominican Republic-Central America- United States Free Trade Agreement Implementation Act, with respect to Costa Rica. (This page is intentionally blank) Annex I Effective with respect to goods that are entered, or withdrawn from warehouse for consumption, on or after January 1, 2009, the Harmonized Tariff Schedule of the United States (HTS) is modified as provided herein, with bracketed matter included to assist in the understanding of proclaimed modifications. The following supersedes matter now in the HTS. (1). General note 4 is modified as follows: (a). by deleting from subdivision (a) the following country from the enumeration of independent beneficiary developing countries: Costa Rica (b).
    [Show full text]