DOCSLIB.ORG

Porsolt Pain Models

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Porsolt Pain Models REV_Leaflet_Pain_210x275mm.qxp_Mise en page 1 30/08/2017 17:26 Page2 Scientist-to-Scientist PAIN MODELS PORSOLT HAS AN EXTENSIVE PORTFOLIO OF SERVICES SUPPORTING DRUG DISCOVERY AND DEVELOPMENT. THE DOMAINS OF ACUTE AND CHRONIC PAIN AND INFLAMMATION ARE ACTIVE AREAS OF RESEARCH AT PORSOLT MATCHING THE NEEDS OF THE INDUSTRY. PORSOLT REMAINS COMMITTED TO MAINTAINING A RECOGNIZED EXPERTISE IN THESE IMPORTANT THERAPEUTIC AREAS BY CONTINUING TO EXPAND ITS BROAD PAIN CAPABILITIES. 7 1 0 2 r e b m e t p e S 1 0 0 . v - d e v r e s e R s t h g i R l l A . A . S t l o s r o P © Compliance www.porsolt.com REV_Leaflet_Pain_210x275mm.qxp_Mise en page 1 30/08/2017 17:26 Page3 PAIN MODELS Acute Pain Neuropathic Pain • Acute nociception in rodents: • Bennett (CCI) model of neuropathic pain in the rat: PINCHMETER | HOT PLATE | TAIL FLICK | COLD PLATE Neuropathic pain develops over the 7 days following chronic loose ligation of the sciatic nerve. Several acute pain assays measuring responses to tactile and thermal stimulation are available in rodents. • Chung (SNL) model of neuropathic pain in the rat: Neuropathic pain develops over the 14 days following chronic Classically, the pinchmeter (alternative method to the Randall and tight ligation of the dorsal root nerve (L5-L6). Selitto test) is used to assess tactile hyperalgesia, while the hot plate, cold plate and tail flick tests evaluate thermal hyperalgesia. MEASURE REFERENCE ROUTE EFFECT* SPECIES REFERENCE ROUTE EFFECT n BENNETT | CHUNG IN THE RAT n PINCHMETER Plantar, Cold Plate, Electronic von Frey, Morphine i.p. 4 Mouse/Rat Morphine i.p. 4 Pinchmeter Mouse/Rat Tramadol p.o. 4 Plantar, Cold Plate, n HOT PLATE Electronic von Frey, Pregabalin p.o. 4 Mouse/Rat Morphine p.o., i.p., s.c., i.v.*, i.t.* 4 Pinchmeter Mouse/Rat Paracetamol i.p., p.o. 4 Mouse Tramadol p.o. 4 Plantar, Cold Plate, Mouse Codeine p.o. 4 Electronic von Frey, Tramadol i.p. 4 Pinchmeter n TAIL FLICK Plantar, Cold Plate, Mouse/Rat Morphine p.o., i.p., s.c., i.v.*, i.t.* 4 Duloxetine p.o. 4 Mouse/Rat Tramadol p.o. 4 Pinchmeter Mouse Codeine p.o. 4 Rat Fentanyl s.c. 4 * Positive effects are observed on selected measures ≥ n COLD PLATE Several pain measures can be used: Mouse/Rat Morphine i.p. 4 - Thermal stimulation (heat hyperalgesia or cold allodynia): Mouse/Rat Tramadol p.o. 4 measured using the Hargreaves method or the cold plate Rat Pregabalin p.o. 4 test (4°C), respectively. * In the mouse only - Tactile stimulation (tactile allodynia or tactile hyperalgesia): measured using an electronic von Frey apparatus or a COLD PLATE TEST IN THE RAT (-3°C) pinch meter. 30 ≥ Optional non-evoked pain measures: s 25 e s n ACTIVITY METER o 160 p s e r 20 l a 140 w 200 a ** r d 120 180 h t 15 i s w ** 160 g f s n o 100 r i s a r 140 s e ** * e r o b 10 r f c m 80 120 o ** * ** * u f r ** * o N * e r 100 b e 60 m b 5 u 80 m N u N 40 60 0 40 20 Vehicle Morphine 12 mg/kg Tramadol 64 mg/kg Pregabalin 100 mg/kg 20 Morphine and vehicle administration i.p. 30 minutes before the test, 0 0 tramadol and pregabalin administration p.o. 60 minutes before the test, Sham rats Bennett/CCI rats Sham rats Chung/SNL rats Sham rats Bennett/CCI rats Sham rats Chung/SNL rats Unpaired Student's t test vs vehicle group: ** = p < 0.01 and *** = p < 0.001, n=10 Student's t test vs sham group: * = p < 0.05 and ** = p < 0.01, n=12 Student's t test vs sham group: *** p < 0.001, n=12 COLD PLATE TEST IN THE MOUSE (-2°C) DYNAMIC WEIGHT BEARING (DW B (1) ) 30.0 25.0 160 s 180 e s n o 160 140 p * s 20.0 e r l 140 120 a ) ) w a g g r ( 120 ( 100 d 15.0 t t h h h t i g 100 Be nnett/CCI mo del g Ch ung/SNL mo del i i w e e 80 f o W W r 10.0 80 e b 60 m 60 u N 40 5.0 40 *** 20 20 0.0 0 0 Vehicle Morphine (12 mg/kg) Tramadol (64 mg/kg) Left forepaw Right forepaw left hindpaw right hindpaw Left forepaw Right forepaw left hindpaw right hindpaw Morphine and vehicle administration i.p. 30 minutes before the test, tramadol administration p.o. 60 minutes before the test, Morphine and vehicle administration i.p. 30 minutes before the test, n=8 or 10 Morphine and vehicle administration i.p. 30 minutes before the test, n=8 or 10 Unpaired Student's t test vs vehicle group: * = p < 0.05 and *** = p < 0.001, n=10 Vehicle morphine 8 mg/kg REV_Leaflet_Pain_210x275mm.qxp_Mise en page 1 30/08/2017 17:26 Page4 Post-Operative Pain Inflammatory Pain • Brennan model of post-operative pain in the rat: • Inflammatory pain in rodents: - A longitudinal incision of skin, fascia and muscle of the plantar - FORMALIN (early and late phase) (rat and mouse) aspect of the rat hindpaw is performed under anesthesia. - CAPSAICIN (rat and mouse) Tactile allodynia, tactile hyperalgesia and thermal hyperalgesia - - CARRAGEENAN MODEL (rat and mouse) can be measured as early as 3 hours after surgery and up to 3-4 afterwards. Rats are injected with carrageenan into the lower surface of the right hindpaw and evaluated at least 2 hours later. (1) - Dynamic Weight Bearing (DWB ) evaluation can also be used. - COMPLETE FREUND’S ADJUVANT MODEL (rat and mouse) MEASURE REFERENCE ROUTE EFFECT Rats are injected with CFA into the lower surface of the right hindpaw and evaluated 24 hours later. n BRENNAN IN THE RAT Electronic von Frey, - CHRONIC INFLAMMATORY PAIN Morphine p.o, i.p., s.c. 4 Plantar, Pinchmeter (CFA-induced monoarthritis) (rat) Rats are injected with a suspension of Mycobacterium Electronic von Frey Ibuprofen p.o. 4 butyricum ( Freund's adjuvant) into the tibio-tarsal joint. Electronic von Frey, Testing phase can be performed 7 and/or 14 days Anandamide i.p. 4 Plantar after induction - OSTEOARTHRITIS: MIA MODEL (rat) SNB Electronic von Frey, Bupivacaine (Sciatic Nerve 4 Monosodium iodoacetate (MIA) is injected through Plantar, Pinchmeter Block) the infra patellar ligament into the joint space of one knee. Testing phase is performed 14 days after induction 120 Brenn an mo del - SURGICAL OSTEOARTHRITIS (guinea-pig) (anterior cruciate 100 ligament ACL transection combined to meniscal lesion) ** * ) 80 g ( t ≥ h Several pain measures can be proposed: g i e 60 W (1) Dynamic - Tactile stimulation (tactile allodynia or tactile hyperalgesia): 40 Weight Bearing measured using an electronic von Frey apparatus or a (DWB) 20 pinchmeter (applied to the paw and to the knee). 0 - Thermal stimulation (heat hyperalgesia): measured using Left forepaw Ri ght forepaw Left h indp aw Right h indpaw the plantar test. Paired Student's t test vs non-lesioned paw: *** = p < 0.001, n=10 BRENNAN MODEL OF POST-OPERATIVE PAIN PINCHMETER TEST (KNEE) IN THE SURGICAL IN THE RAT: EFFECTS OF MORPHINE 24 HOURS OSTEOARTHRITIS MODEL IN GUINEA-PIG AFTER SURGERY 50 Thermal hyperalgesia (Plantar) 1000 45 *** Tactile allodynia (Electronic von Frey) ) 900 g ( ) 40 s 70 l ( a y ) c w g 35 n ( a 800 r e l 60 t d a a l h w t l 30 i a a r 50 w - 700 w d h a w t r 25 i a d w p h 40 t i w ** g 600 a w 20 ### - n p ** i w c * g 30 a u n P i *** 15 d c n 500 ** u i d 20 e n *** i ### 10 c r *** e o c F r 400 o 10 5 F 0 0 300 Vehicle Morphine 64 mg/kg Vehicle Morphine 64 mg/kg Baseline D7 D14 D21 D28 D42 Baseline D7 D14 D21 D28 D42 Morphine administration p.o. 60 minutes before the test Morphine administration p.o. 60 minutes before the test Sham Operated Paired Student's t test vs non-lesioned paw: ### = p < 0.001, Paired Student's t test vs non-lesioned paw: ### = p < 0.001, Unpaired Student's t test vs vehicle group: ** = p < 0.01, n=10 Unpaired Student's t test vs vehicle group: *** = p < 0.001, n=10 Paired Student's t test vs non-lesioned paw: * = p < 0.05, ** = p < 0.01 and *** = p < 0.001, n=10 or 20 1200 ) g Tactile hyperalgesia (Pinchmeter) ( l *** a 1000 w *** a r *** d h t 800 i *** w w a p 600 Non-lesioned paw g n *** i c ### u 400 Lesioned paw d n i e c r 200 o F 0 Vehic le Morphine Morphine Mo rphine 10 4 mg/kg 8 mg/kg 16 mg/kg Morphine administration i.p. 30 minutes before the test Paired Student's t test vs non-lesioned paw: ### = p < 0.001, Unpaired Student's t test vs vehicle group: *** = p < 0.001, n=10 REV_Leaflet_Pain_210x275mm.qxp_Mise en page 1 30/08/2017 17:26 Page1 PAIN MODELS Visceral Pain Inflammation • Acetic acid or Parabenzoquinone-induced • YEAST HYPERTHERMIA writhing in the mouse: • LPS SEPTIC SHOCK - Animals are injected with acetic acid or parabenzoquinone (i.p.). • AIR POUCH - The number of writhes is counted for 10 minutes, beginning 5 minutes after the injection of reagent substance.
Load more

Recommended publications
  • Neuropathic Component of Low Back Pain of Low Back Component Neuropathic +2 ) Enters Into Cell
    229 NEUROPATHIC Aspects Spine Surgery: Current Minimally Invasive COMPONENT OF LOW BACK PAIN 36 Simin Hepguler MD month study period, it was estimated that direct re- Introduction source cost was 96 million $ for patients with CLBP and neuropathic component of CLBP accounted for ow back pain is a frequent problem of mus- 96% of the total cost. Cost of care is 160% higher for culo-skeletal system. Life-long prevalence is patients with CLBP associated with NP than patient 60-85% and the incidence is 15% (12-30%) in with CLBP not associated with NP. CLBP with NP L26 adults. Although underlying cause is not known component is found in 4% of German adult popula- in most cases, compression fracture was found in tion. Care cost of neuropathic low back pain is 67% 4% of all low back pain cases, while spondylolisthe- higher than care cost of nociceptive pain. Of the to- sis, tumor or metastasis, ankylosing spondylitis and tal care cost of low back pain, 16% is reserved for infection were determined in 3%, 0.07%, 0.3% and neuropathic component.39 0.01%, respectively. It was also found that remain- ing cases were secondary to mechanical spraining of structures forming the lumbar region.26 Definition This is the most common and most expensive Low back pain is felt in a region ranging from in- reason of occupation-related disability in subjects ferior margin of rib cage to waistline; the pain can who are aged <45 years. The estimated direct cost be localized in lumbar region, but it may also radi- of the condition was 1.6 billion £ and the total cost ate to the leg.
    [Show full text]
  • Recognition and Alleviation of Distress in Laboratory Animals
    http://www.nap.edu/catalog/11931.html We ship printed books within 1 business day; personal PDFs are available immediately. Recognition and Alleviation of Distress in Laboratory Animals Committee on Recognition and Alleviation of Distress in Laboratory Animals, National Research Council ISBN: 0-309-10818-7, 132 pages, 6 x 9, (2008) This PDF is available from the National Academies Press at: http://www.nap.edu/catalog/11931.html Visit the National Academies Press online, the authoritative source for all books from the National Academy of Sciences, the National Academy of Engineering, the Institute of Medicine, and the National Research Council: x Download hundreds of free books in PDF x Read thousands of books online for free x Explore our innovative research tools – try the “Research Dashboard” now! x Sign up to be notified when new books are published x Purchase printed books and selected PDF files Thank you for downloading this PDF. If you have comments, questions or just want more information about the books published by the National Academies Press, you may contact our customer service department toll- free at 888-624-8373, visit us online, or send an email to [email protected]. This book plus thousands more are available at http://www.nap.edu. Copyright © National Academy of Sciences. All rights reserved. Unless otherwise indicated, all materials in this PDF File are copyrighted by the National Academy of Sciences. Distribution, posting, or copying is strictly prohibited without written permission of the National Academies Press. Request reprint permission for this book. Recognition and Alleviation of Distress in Laboratory Animals http://www.nap.edu/catalog/11931.html Recognition and Alleviation of Distress in Laboratory Animals Committee on Recognition and Alleviation of Distress in Laboratory Animals Institute for Laboratory Animal Research Division on Earth and Life Studies THE NATIONAL ACADEMIES PRESS Washington, D.C.
    [Show full text]
  • Developing Concepts in Allodynic Pain
    I CONFERENCE REPORTS Developing concepts in allodynic pain NG Shenker, HC Cohen and DR Blake Allodynia is the perception of pain in response to Phenomena (eg pain) instruct explanatory theories. NG Shenker1 stimuli that are not normally painful. The manage- These theories change the observed expression of the PhD MRCP, ment of patients with chronic pain and allodynia is original phenomena. Pain can be classified in a similar Consultant suboptimal, partly because of social stigmatisation. manner to visual experiences and this will permit a Rheumatologist Patients are made to feel that they are malingering or new understanding of its expression. HC Cohen2,3 looking for secondary gain. Unfortunately, the legal What immediate implication does this framework MRCP, arc Research profession often propagates this myth and the adver- have? Acute pain drives the subject to respond imme- Fellow and sarial nature of the courts contributes negatively to diately to an external object. Chronic pain is associ- Honorary the patient’s situation. Remarkable recent under- ated with cognitive deficits such as short-term Consultant standings of profound brain changes occurring in memory loss and poor concentration. Chronic pain DR Blake2,3 chronic pain patients will challenge the way that such also affects behaviour without the patient’s aware- FRCP, Professor of medicolegal cases are decided. This ground-breaking ness. The pain matrix intimately involves structures Locomotor conference related expertise and experiences from in the brain related to emotions and these are Medicine patients, clinicians and leading scientists in this field intrinsic to the experience. All of these examples 1Addenbrookes and was the fourth conference in an interdisciplinary are of brain reception and perception rather than Hospital, series centred around pain and suffering organised conception (explicit understanding).
    [Show full text]
  • Botulinum Toxin Treatment for Intractable Allodynia in a Patient with Complex Regional Pain Syndrome: a Case Report
    Neurology Asia 2020; 25(2) : 215 – 219 Botulinum toxin treatment for intractable allodynia in a patient with complex regional pain syndrome: A case report Hyunseok Kwak MD, Dong Jin Koh MD, Kyunghoon Min MD PhD Department of Rehabilitation Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea Abstract The right hand of a 58-year-old female was compressed by a compression machine and subsequently began to show pain. She was diagnosed with complex regional pain syndrome type 2 according to the Budapest criteria. Conventional therapy was ineffective for her allodynia. After subcutaneous injection of botulinum toxin, the subject’s allodynia substantially improved. Subcutaneous injection of botulinum toxin could effectively treat patients with complex regional pain syndrome and intractable allodynia. Clinical studies with larger sample sizes are needed to evaluate the efficacy of and selection of patients for botulinum toxin treatment of complex regional pain syndrome. Keywords: Complex regional pain syndrome, botulinum toxin, pain, allodynia INTRODUCTION complex pathogenesis and heterogenous clinical spectrums associated with CRPS. Hyperalgesia Complex regional pain syndrome (CRPS) is and allodynia are key clinical features of CRPS.12 a distressing pain disorder that presents as This report describes a patient for whom BTX disparate changes in sensory, vasomotor, or treatment was effective in relieving severe motor systems, as well as edema.1 Few cases of allodynia associated with CRPS. CRPS resolve within 12 months of onset, while most patients suffer from unremitting pain and CASE REPORT devastating disability.2 Despite varied pain control management strategies, there is no cure and A 58-year-old female was referred for the outcomes remain less optimistic.
    [Show full text]
  • NOCICEPTORS and the PERCEPTION of PAIN Alan Fein
    NOCICEPTORS AND THE PERCEPTION OF PAIN Alan Fein, Ph.D. Revised May 2014 NOCICEPTORS AND THE PERCEPTION OF PAIN Alan Fein, Ph.D. Professor of Cell Biology University of Connecticut Health Center 263 Farmington Ave. Farmington, CT 06030-3505 Email: [email protected] Telephone: 860-679-2263 Fax: 860-679-1269 Revised May 2014 i NOCICEPTORS AND THE PERCEPTION OF PAIN CONTENTS Chapter 1: INTRODUCTION CLASSIFICATION OF NOCICEPTORS BY THE CONDUCTION VELOCITY OF THEIR AXONS CLASSIFICATION OF NOCICEPTORS BY THE NOXIOUS STIMULUS HYPERSENSITIVITY: HYPERALGESIA AND ALLODYNIA Chapter 2: IONIC PERMEABILITY AND SENSORY TRANSDUCTION ION CHANNELS SENSORY STIMULI Chapter 3: THERMAL RECEPTORS AND MECHANICAL RECEPTORS MAMMALIAN TRP CHANNELS CHEMESTHESIS MEDIATORS OF NOXIOUS HEAT TRPV1 TRPV1 AS A THERAPEUTIC TARGET TRPV2 TRPV3 TRPV4 TRPM3 ANO1 ii TRPA1 TRPM8 MECHANICAL NOCICEPTORS Chapter 4: CHEMICAL MEDIATORS OF PAIN AND THEIR RECEPTORS 34 SEROTONIN BRADYKININ PHOSPHOLIPASE-C AND PHOSPHOLIPASE-A2 PHOSPHOLIPASE-C PHOSPHOLIPASE-A2 12-LIPOXYGENASE (LOX) PATHWAY CYCLOOXYGENASE (COX) PATHWAY ATP P2X RECEPTORS VISCERAL PAIN P2Y RECEPTORS PROTEINASE-ACTIVATED RECEPTORS NEUROGENIC INFLAMMATION LOW pH LYSOPHOSPHATIDIC ACID Epac (EXCHANGE PROTEIN DIRECTLY ACTIVATED BY cAMP) NERVE GROWTH FACTOR Chapter 5: Na+, K+, Ca++ and HCN CHANNELS iii + Na CHANNELS Nav1.7 Nav1.8 Nav 1.9 Nav 1.3 Nav 1.1 and Nav 1.6 + K CHANNELS + ATP-SENSITIVE K CHANNELS GIRK CHANNELS K2P CHANNELS KNa CHANNELS + OUTWARD K CHANNELS ++ Ca CHANNELS HCN CHANNELS Chapter 6: NEUROPATHIC PAIN ANIMAL
    [Show full text]
  • Global Year Against Neuropathic Pain
    2014-2015 Allodynia and Hyperalgesia in Neuropathic Pain Allodynia and hyperalgesia are common and bothersome symptoms in patients with pain due to a disease or injury of the nervous system. Definition Allodynia is pain due to a stimulus that does not normally elicit pain. Hyperalgesia is increased pain from a stimulus that normally provokes pain. Clinical manifestations • Allodynia and hyperalgesia are clinical terms that do not imply a mechanism. • The clinical presentation differs between the different pain conditions. • The distribution of allodynia and hyperalgesia is located within, but occasionally extends beyond, the innervation territory of the injured or diseased nervous structure. • Onset is usually early and may decrease over time following an acute injury but may increase over time in slowly progressing neuropathic pain conditions. Early hypersensitivity may increase the odds for persistent neuropathic pain. Classification • Allodynia and hyperalgesia are classified according to the sensory modality that elicits pain, i.e. thermal (cold and heat) or mechanical (dynamic touch, punctuate, and pressure). • Dynamic mechanical allodynia is pain evoked by light brushing or stroking of the skin. • Pressure (static and deep pressure) allodynia and hyperalgesia are elicited by pressure to skin and deep tissue). • Punctate allodynia and hyperalgesia are evoked by punctate skin stimulation by a pin or a monofilament. • Cold and warm allodynia and hyperalgesia are provoked by cold or warm stimuli applied to the skin. Clinical assessment • Simple bedside tests include response (pain intensity and character) to cotton swab, finger pressure, pinprick, cold and warm stimuli, e.g., metal thermo rollers at 20 and 40oC, as well as mapping of the area of abnormality.
    [Show full text]
  • Hyperalgesia and Allodynia: Peripheral Mechanisms
    Joint Bone Spine 72 (2005) 359–371 http://france.elsevier.com/direct/BONSOI/ Review Hyperalgesia and allodynia: peripheral mechanisms Anne Coutaux a, Frédéric Adam b,c, Jean-Claude Willer d,*, Daniel Le Bars b a Rheumatology Department, Pitié-Salpêtrière Teaching Hospital, 91, Boulevard de l’Hôpital, 75013, Paris, France b Inserm E-0331 Research Unit, Pitié-Salpêtrière School of Medicine and Teaching Hospital, 91, Boulevard de l’Hôpital, 75013, Paris, France c Anaesthesia and Intensive Care Unit, Ambroise Paré Teaching Hospital, 9 Av Charles de Gaulle, 92100 Boulogne-Billancourt, France d Inserm E-0349 Research Unit and Neurophysiology Laboratory, Pitié-Salpêtrière School of Medicine and Teaching Hospital, 91, Boulevard de l’Hôpital, 75013, Paris, France Received 30 June 2003; accepted 8 January 2004 Available online 23 July 2004 Abstract Nociceptive signals are generated by peripheral sensory organs called nociceptors, which are endings of small-diameter nerve fibers responsive to the tissue environment. The myriad chemical mediators capable of activating, sensitizing, or arousing nociceptors include kinins, proinflammatory and anti-inflammatory cytokines, prostanoids, lipooxygenases, the “central immune response mediator” NF-jB, neurotrophins and other growth factors, neuropeptides, nitric oxide, histamine, serotonin, proteases, excitatory amino acids, adrenergic amines, and opioids. These mediators may act in combination or at a given time in the inflammatory process, producing subtle changes that result in hyperalgesia or allodynia. We will review the most extensively studied molecular and cellular mechanisms underlying these two clinical abnormalities. The role of the peripheral nervous system in progression of inflammatory joint disease to chronicity is discussed. © 2005 Elsevier SAS. All rights reserved.
    [Show full text]
  • National MS Society Clinical Bulletin
    Clinical Bulletin Information for Health Professionals Pain in Multiple Sclerosis Heidi Maloni, PhD, ANP-BC, CNRN, MSCN INTRODUCTION “….pain is almost never just a pain. The ripples spread from the nervous system into the sufferer’s whole life. The kind of pain that is recurring or chronic has an impact on the patient’s personality and relationship with the world. Pain does not happen in a laboratory. It happens to an individual, and there is a cultural context that informs the individual’s experience. What a pain is, and whether it matters, is not just a medical question”. - Hilary Mantel, 2013 ain is not just a medical question as pain has potential to change the individual sufferer and influence their psychological, social and spiritual being. Pain, when it occurs in association with multiple sclerosis, is an important symptom with risk for mood disorders, social isolation and worsening pain. The MS pain experience is individual, expressed in very personal and subjective terms. “My pain dominates. The burning in my feet so intense, I rub the skin off my knees to relieve it” (Robert, personal conversation). “The pain depresses me. I do not even want to get out of bed. Sadly, my husband’s touch makes the pain worse,” (Barbara, MS patient encounter). “Ice cold water is running down my legs at the same time my thighs are on fire….how can both of those feelings exist?” (Connie, MS patient encounter). “I don’t think I can live like this anymore. My pain consumes me. The drugs help less and less and I fear the day when they will no longer work at all.
    [Show full text]
  • Practical Considerations in Analgesic Selection for Chronic Noncancer Pain
    Primary Care Pain Management in Pennsylvania: Optimizing Treatment, Minimizing Risk PRACTICAL CONSIDERATIONS IN ANALGESIC SELECTION FOR CHRONIC NONCANCER PAIN MARY LYNN MCPHERSON, PHARMD, MA, BCPS, CPE UNIVERSITY OF MARYLAND SCHOOL OF PHARMACY . LEARNING OBJECTIVES 1. Given an actual or simulated patient with chronic noncancer pain, demonstrate consideration of patient- and drug-related variables in selecting opioid analgesics. 2. Demonstrate competence in basic opioid conversion calculations and opioid dosage titration. 3. Given an actual or simulated patient with chronic noncancer pain, recommend appropriate coanalgesic. WHAT IS PAIN? ¡ “Total” Pain (Dame Cicely Saunders) ¡ Physical (due to disease or treatments) ¡ Psychological (anger, fear of suffering, depression, past experience of illness) ¡ Social (loss of role, status, job; financial concerns, worries about future/ family, dependency) ¡ Spiritual (anger, loss of faith, finding meaning, fear of the unknown ¡ An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage (IASP). ¡ “Pain is whatever the person experiencing it says it is” (McCaffery). www.iasp-pain.org/AM/Template.cfm?Sec8on=Home&Template=/CM/ContentDisplay.cfm&ContentID=8705 PATHOGENESIS OF PAIN Pain Nocicep8ve Neuropathic Central or Visceral Somac Peripheral Type of pain How patient’s describe it Analgesics Nociceptive • May be sharp or dull, often aching in nature Responds well to somatic pain • Familiar pain (e.g., toothache) primary analgesics
    [Show full text]
  • A Role for ASIC3 in the Modulation of High-Intensity Pain Stimuli
    A role for ASIC3 in the modulation of high-intensity pain stimuli Chih-Cheng Chen*, Anne Zimmer*†, Wei-Hsin Sun*, Jennifer Hall*, Michael J. Brownstein*, and Andreas Zimmer*†‡ *Laboratory of Genetics, National Institute of Mental Health, 36 Convent Drive 3D06, Bethesda, MD 20892; and †Laboratory of Molecular Neurobiology, Department of Psychiatry, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany Communicated by Jean-Pierre Changeux, Institute Pasteur, France, April 24, 2002 (received for review February 18, 2002) Acid-sensing ion channel 3 (ASIC3), a proton-gated ion channel of neurons such as a reduced sensitivity of some mechanoreceptors the degenerins͞epithelial sodium channel (DEG͞ENaC) receptor to noxious pinch and an enhanced sensitivity to light touch (6). family is expressed predominantly in sensory neurons including However, the contribution of ASIC3 to pain signaling remains nociceptive neurons responding to protons. To study the role of unclear. In this study we show that ASIC3Ϫ͞Ϫ animals display ASIC3 in pain signaling, we generated ASIC3 knockout mice. enhanced behavioral responses to high-intensity nociceptive Mutant animals were healthy and responded normally to most stimuli regardless of their modality. These results reveal a role sensory stimuli. However, in behavioral assays for pain responses, for ASIC3 in the tonic inhibition of high-intensity pain signals. ASIC3 null mutant mice displayed a reduced latency to the onset of pain responses, or more pain-related behaviors, when stimuli of Materials and Methods -moderate to high intensity were used. This unexpected effect Generation and Breeding of ASIC3؊͞؊ Mice. Genomic clones con seemed independent of the modality of the stimulus and was taining the mouse ASIC3 gene were screened from a 129͞Sv observed in the acetic acid-induced writhing test (0.6 vs.
    [Show full text]
  • Neuropathic Pain
    WSAVA Global Pain Council Pain Management Protocol The following pain management protocol is tiered to ensure a global relevance, recognizing that not all analgesic modalities are available to veterinary practitioners and vary from region to region around the world. Its implementation will be guided by the various analgesic modalities available along with the needs of the individual patient requiring treatment. This protocol is reproduced from the WSAVA Global Pain Treatise, a succinct yet comprehensive review of pain assessment, various pain modalities, and the treatment of various clinically painful scenarios in both dogs and cats. The WSAVA GPC Pain Treatise published in the Journal of Small Animal Practice and is available for open access at the GPC pages of www.wsava.org. Neuropathic pain Neuropathic pain requires several classes of medications and procedures as it cannot be adequately managed with a single pharmacological or non-pharmacological therapy. Prior to, and during any surgical procedure, various dierent analgesic drugs and modalities can be used to reduce the inciting nociceptive aerent impulse. Many of these are continued postoperatively to reduce both peripheral (PNS) and central (CNS) sensitization. NSAIDs ere is evidence to support an inammatory response driving the pathophysiological changes of the peripheral and central nervous systems resulting in neuropathic pain and augmentation of pain processing by spinal prostanoids. While no studies are reported at this time, human clinical trials are currently underway investigating various modalities to target specic components of the neuroinammatory process. It is advised that NSAIDs be used in the treatment of neuropathic pain. Opioids Opioids may be included in a multimodal regimen to manage neuropathic pain, but not as a stand alone analgesic.
    [Show full text]
  • Maldynia: Pathophysiology and Management of Neuropathic and Maladaptive Pain—A Report Of
    Pain Medicine 2010; 11: 1635–1653 Wiley Periodicals, Inc. REVIEW ARTICLE Maldynia: Pathophysiology and Management of Neuropathic and Maladaptive Pain—A Report of the AMA Council on Science and Public Healthpme_986 1635..1653 Barry D. Dickinson, PhD,* C. Alvin Head, MD,† viewed as maladaptive because it may occur in the Stuart Gitlow, MD,‡ and Albert J. Osbahr, III, MD§ absence of ongoing noxious stimuli and does not promote healing and repair. *Council on Science and Public Health, American Medical Association, Chicago, Illinois; Objective. To address recent findings on the patho- genesis of pain following neural injury and consider whether the development of maladaptive pain justi- †Department of Anesthesiology and Perioperative fies its classification as a disease and to briefly Medicine, Medical College of Georgia, Augusta, discuss the scope of pharmacologic and non- Georgia; pharmacologic approaches employed in patients with such pain. ‡Department of Psychiatry, Mount Sinai School of Medicine, New York; Methods. English language reports on studies using human subjects were selected from a PubMed search §Occupational Services, Catawba Valley Medical of the literature from 1995 to August 2010 and from the Cochrane Library. Further information was Center, Hickory, North Carolina, USA obtained from Internet sites of medical specialty and other societies devoted to pain management. Reprint requests to: Barry D. Dickinson, PhD, American Medical Association, 515 North State Street, Results. Neural damage to either the peripheral Chicago, IL 60654, USA. Tel: 312-464-4549; Fax: or central nervous system provokes multiple 312-464-5841; E-mail: [email protected]. processes including peripheral and central sensiti- For the Council on Science and Public Health, zation, ectopic activity, neuronal cell death, disinhi- American Medical Association.
    [Show full text]