The Neurobiology, Physiology, and Psychology of Pain

1st Edition - November 9, 2021
Editors: Rajkumar Rajendram, Victor R Preedy, Vinood Patel, Colin R Martin
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 2 0 5 8 9 - 1
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 2 0 6 0 8 - 9

The Neurobiology, Physiology and Psychology of Pain focuses on bettering readers’ understanding of acute and chronic pain. Featuring chapters on neurotransmitters, pharmacol… Read more

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The Neurobiology, Physiology and Psychology of Pain focuses on bettering readers’ understanding of acute and chronic pain. Featuring chapters on neurotransmitters, pharmacology, and brain imaging, this volume discusses, in detail, the mechanisms of pain and experimental studies undertaken to better understand the pathways involved. The translational work in this area has applicability for neurologists, anesthesiologists, pharmacologists, and anyone working in the intersection of these areas. This volume is integral for anyone interested in the molecular underpinnings of pain at every level.

Cover image
Title page
Table of Contents
Copyright
Contributors
Preface
Part I: Molecular and cellular aspects
Chapter 1: KCNQ/Kv7 channels as therapeutic target to treat neuropathic pain
Abstract
Introduction
KCNQ/Kv7 channel family members
KCNQ channels in primary sensory neurons and their contribution to neuropathic pain
KCNQ channels as therapeutic target to treat neuropathic pain
Applications to other areas
Other agents of interest
Mini-dictionary of terms
Key facts of KCNQ/Kv7 channels and neuropathic pain
Summary points
Chapter 2: A new mutation in NTRK1 gene is associated with congenital insensitivity to pain without anhidrosis
Abstract
Introduction
The applications to other areas
Mini-dictionary of terms
Key facts
Summary points
Chapter 3: Prdm12, a key transcriptional regulator of the nociceptive lineage
Abstract
Introduction
Applications to other areas
Other agents of interest
Mini-dictionary of terms
Key facts showing the importance of Prdm12 in nociceptors
Summary points
Chapter 4: Genetics of chronic widespread musculoskeletal pain
Abstract
Introduction
Heritability of chronic widespread musculoskeletal pain
Candidate gene studies in chronic widespread musculoskeletal pain
GWAS
Interactions (gene-gene and gene-environment)
Future perspectives (mainly, research agenda)
Applications to other areas
Mini-dictionary of terms
Key facts
Summary points
Chapter 5: Fentanyl: Polymorphisms, and adverse events
Abstract
Opioid fentanyl use in pain management
Potential pharmacogenetics markers in fentanyl pain management
Barriers to implementation
Conclusions
Applications to other areas
Other agents of interest
Mini-dictionary of terms
Key facts of fentanyl
Summary points
Chapter 6: Propofol anesthesia and molecular changes in the brain
Abstract
Introduction
Formulation matter
Neural and molecular targets of propofol
Propofol-induced brain molecular changes during postanesthesia period
Molecular autograph of longer exposures to propofol at the peak of the brain growth spurt
Propofol and age-related brain pathology
Applications to other areas
Other agents of interest
Mini-dictionary of terms
Key facts of propofol anesthesia and molecular changes in the brain
Summary points
Chapter 7: Protein kinase G is a molecular switch for pain
Abstract
Introduction
Pain is perceived via inputs from nociceptive circuits that are adaptive
LTH is induced by protein kinase G, a positive injury signal in nociceptive neurons
Development of a novel potent PKG inhibitor
Conclusions
Applications to other areas
Other agents of interest
Mini-dictionary of terms
Key facts
Summary points
Chapter 8: Adrenergic agonists and antagonists enhance opioid receptor activity
Abstract
Introduction
Anatomical and cellular codistribution of opioid and adrenergic functions
Mechanisms of adrenergic receptor-opioid receptor cross-talk
A model of adrenoceptor-opioid receptor cross-talk
Synergistic effects of adrenergic-opioid receptor cross-talk in the treatment of pain
Prevention of desensitization and mutual resensitization of opioid and adrenergic receptor function by each other’s ligands
Applications to other areas: Local anesthetic enhancement and opioid sparing uses
Other agents of interest: Ascorbic acid, tramadol and tapentadol, and ketamine
Mini-dictionary of terms
Key facts
Summary points
Chapter 9: Inflammatory and neuropathic pain impact on the opioid function in the mesocorticolimbic system
Abstract
Introduction
A short introduction to the opioid receptors
The endogenous opioid system: A key component of analgesia, reward, and aversion
Chronic pain alters brain function and connectivity recruiting motivational and emotional regions
PET imaging confirms pain-induced alterations of ORs in the MCLS during pain
Preclinical studies show altered MOR density or function derived from the presence of pain
Animal models of pain showed altered DA-related behaviors derived from the pharmacological activation of MORs
Inflammatory pain promotes increased opioid self-administration
Dynorfin/KOR system (Dyn/KOR) of the MCLS: A new key player in pain field
Applications to other areas
Mini-dictionary of terms
Key facts of pain-induced changes in OR function
Summary points
Chapter 10: Clinacanthus nutans L., analgesia, and the l-arginine/nitric oxide-mediated/cyclic-guanosine monophosphate-independent pathway
Abstract
Introduction
Clinacanthus nutans L.
Report on findings related to the antinociceptive activity of C. nutans
Antinociceptive profile of PEP and the possible mechanisms of antinociception
Phytoconstituents of MCNL and PEP
Conclusion based on the reported antinociceptive activity of MCNL and PEP
Involvement of peripheral and central antinociceptive mechanisms
Involvement of various mechanisms of antinociception
Involvement of specific opioidergic system subtypes
Role of nonopioidergic systems
Involvement of transient receptor potential vanilloid type 1 (TRPV1) receptors, glutamatergic system, protein kinase C (PKC)-mediated pathway, and bradykininergic system
Involvement of α2-adrenergic, β-adrenergic, adenosinergic, dopaminergic, or muscarinic cholinergic receptor systems
Involvement of various types of K+ channels
Role of NO-mediated pathways
Applications to other areas
Other agents of interest
Mini-dictionary of terms
Key facts
Summary points
Chapter 11: The orally bioavailable imidazodiazepine, KRM-II-81, is a novel potentiator of α2/3-containing GABAA receptors with analgesic efficacy
Abstract
Introduction
GABA receptors
GABAA receptor potentiating benzodiazepines and pain
Alpha 2/3-containing GABAA receptors
KRM-II-81
KRM-II-81 and pain
Side effect burden
Applications to other therapeutic areas
Other agents of interest
Mini-dictionary of terms
Key facts
Summary points
Chapter 12: Extrasynaptic α5GABAA receptors and their role in nociception and pathological pain
Abstract
Acknowledgments
Introduction
GABAA receptors
Expression of α5GABAA receptors at spinal cord and DRG
GABAergic tonic current in the spinal cord
GABAergic tonic current in spinal cord in mammals
Extrasynaptic α5GABAA receptors in the rate-dependent depression (RDD) of the Hoffmann reflex (HR)
Function of extrasynaptic α5GABAA receptors in primary afferent fibers
Extrasynaptic spinal α5GABAA receptors in pain
Extrasynaptic α5GABAA receptors regulation
Applications to other areas
Other agents of interest
Mini-dictionary of terms
Key facts on α5GABAA receptors in pain
Summary points
Chapter 13: ATP-sensitive potassium channels in pain and analgesia
Abstract
ATP-sensitive potassium channels (Katp)
Possible role for Katp channels in primary nociceptive neurons during hyperglycemia
Katp involvement in the mechanisms of analgesic substances
Application to other areas
Other agents of interest
Mini-dictionary of terms
Key facts
Summary points
Chapter 14: Astrocyte-neuron lactate shuttle and pain
Abstract
Introduction
Applications to other areas
Other agents of interest
Mini-dictionary of terms
Key facts
Summary points
Chapter 15: Nociception and sweet solutions: Applications to inflammatory pain
Abstract
Introduction
Inflammatory pain pathways
Pain behaviors and assessment
Use of sweet solutions for inflammatory pain
Mechanisms of sweet solutions for inflammatory pain
Sweet tasting solutions used for analgesia
Clinical applications
Importance of treatment of neonatal pain
Applications to other areas
Other agents of interest
Other agents of interest
Mini-dictionary of terms
Key facts
Summary points
Chapter 16: Interlinking interleukin-33 (IL-33), neuroinflammation and neuropathic pain
Abstract
IL-33
Neuropathic pain and glial cells
IL-33 and glial cells
Applications to other areas
Other agents of interest
Mini-dictionary of terms
Key facts of IL-33 in neuropathic pain
Summary points
Chapter 17: Neurons of the parabrachial nucleus, nociceptive input, and pain pathways
Abstract
Introduction
Anatomy of the PBN
Afferent pain transmitting pathways to the LPB
Nociceptive neurons in the LPB and their aversive pathway to amygdala and bed nucleus of the stria terminalis (BNST)
CGRP-positive neurons in the PBel
Nociceptive neurons in the LPB and their autonomic connection with the hypothalamus
Pain-modulating pathways from the LPB
Conclusion
Applications to other areas
Mini-dictionary of terms
Summary points
Chapter 18: Anterior cingulate cortex, pain perception, and pathological neuronal plasticity during chronic pain
Abstract
Introduction
ACC is a critical hub linking neuronal circuits for nociception and emotion
ACC activation is associated with the affective component of pain
ACC neuronal activity mediates pain-induced negative affect
Nociception-related neurons in the ACC
Distinct cortical representation of acute and chronic pain
Pathological neuronal plasticity in the ACC associated to chronic pain
Applications to other areas
Other agents of interest
Mini-dictionary of terms
Key facts
Summary points
Chapter 19: Sleep deprivation, headache, and Fos immunohistochemistry
Abstract
Introduction
Pain, headache, and sleep deprivation
The pathophysiologic relationship between sleep deprivation and headache
Modulation of headache and sleep-wake cycles
Pharmacologic relationships between headache and sleep
Experimental research to examine headache and sleep deprivation
Experimental studies of sleep deprivation and headache pain
Applications to other areas
Mini-dictionary of terms
Key facts
Summary points
Chapter 20: Antinociceptive glucagon-like peptides
Abstract
Introduction to the glucagon-like peptides
Applications to other areas
Glucagon-like peptide-1 and its analogs
Glucagon-like peptide-2
Other agents of interest
Mini-dictionary of terms
Key facts of glucagon-like peptides
Summary points
Chapter 21: Pain transmission and peripheral group III metabotropic glutamate receptors (mGluRs)
Abstract
Introduction
Glutamate metabolism in peripheral nervous system
Glutamate release and pain
Glutamate receptor signaling: iGluR and mGluR
Localization of peripheral group III mGluR
Negative modulation of pain transmission
Group III mGluRs in non-neuronal glial cells
Applications to other areas
Other agents of interest
Mini-dictionary of terms
Key facts of activity-dependent inhibition
Summary points
Chapter 22: TRPM8 receptor and menthol in pain management
Abstract
Introduction
Transient receptor potential channels
Menthol
Multimodal pain therapy
Posttraumatic and postoperative pain
Musculoskeletal pain
Neuropathic pain
Headache and migraine
Pregnant and lactating women
Children and adolescent
Elderly
Obesity
Other agents of interest
Applications to other areas
Mini-dictionary of terms
Key facts of TRPM8 receptor and menthol
Summary points
Part II: Physiology, imaging and physical recordings
Chapter 23: Anesthetic and proconvulsant effects of ketamine on EEG
Abstract
Introduction
Ketamine effects as anesthetic
Ketamine effects as proconvulsant
EEG analysis of ketamine effects
Scalp vs intracranial EEG effects of ketamine in nonhuman primate model of an idiopathic generalized epilepsy
Effects of other agents on EEG
Key facts of anesthetic and proconvulsant effects of ketamine on EEG
Summary points
Chapter 24: Electroencephalography and anesthetic doses of ketamine
Abstract
Introduction
Spectral EEG changes
Applications to other areas
Other agents of interest
Mini dictionary of terms
Key facts
Summary points
Chapter 25: Linking heart function and analgesia
Abstract
Introduction
Analgesic drugs
Application to other areas: Effects of NSAIDs on the kidney
Other agents of interest: Adjuvants
Mini-dictionary of terms
Summary points
Chapter 26: Computed tomography-guided procedures for epidural injections
Abstract
Introduction
General principles and technique common to all types of CT-guided epidural injections
Epidural injections
Radiation safety
Complications
Conclusion
Applications to other areas
Other agents of interest
Mini-dictionary of terms
Key facts
Summary points
Chapter 27: Chronic pain: Linking deep brain stimulation and sensory functional MRI
Abstract
Introduction
History of deep brain stimulation for chronic pain
Central pain processing
Modern visualization of DBS targets
Application to other areas
Other methods of interest
Mini-dictionary of terms
Key facts
Summary points
Chapter 28: Neurocognition and placebo analgesia: Linking in functional magnetic resonance imaging
Abstract
Introduction
Understanding the placebo effect: From the biological approach to the advent of neuroimaging techniques
Pain modulatory mechanisms relevant for the neuroimaging study of PA
Pain and nociceptive stimuli in neuroimaging study of PA
Pain evaluation and temporal phases in neuroimaging study of PA
Sample characteristic relevant for the neuroimaging study of PA
Neurocognitive predictors in neuroimaging study of PA: Attention, expectation, and reappraisal
The neuroimaging meta-analytic approach to the study of PA and related neurocognitive factors
Neuroimaging findings in the study of PA in Alzheimer’s disease
Future directions
Applications to other areas
Other agents of interest
Mini-dictionary of terms
Key facts of functional magnetic resonance imaging
Summary points
Chapter 29: Linking the cortex, functional spectroscopy, and pain: Features and applications
Abstract
Basic concepts
Cortical functions related to pain processing
Role of the motor cortex in pain processing
Role of the PFC in pain processing
Nature of brain regions recruited during pain: Insights from human imaging studies
The biological rationale behind near-infrared spectroscopy
fNIRS neuroimaging: Technical aspects, advantages, limitations, and applications
The sequence of steps to perform neuroscience studies using fNIRS
Applications of fNIRS in pain research
fNIRS and cortical connectivity in pain research
Remarks and future directions
Applications to other areas
Mini-dictionary of terms
Key factors related to fNIRS
Summary points
Chapter 30: Muscle origins of myofascial pain syndrome
Abstract
Introduction
Nociception in muscle tissue
Referred pain and peripheral sensitization process
Sympathetic facilitation of muscle pain
Central sensitization
Clinical applications
Conclusion
Application to other areas
Other agents of interest
Mini-dictionary of terms
Key facts of myofascial pain
Summary points
Part III: Psychology and behavior
Chapter 31: Behavioral markers of pain: Understanding the cognitive, motor, and societal interactions in the pain experience
Abstract
Psychology and cognition
Motor behavior
Social interactions and pain behavior convention
What is coming in the next 5–10 years?
Conclusion
Application to other areas
Other agents of interest
Mini-dictionary of terms
Key facts
Summary points
Chapter 32: Adverse life events, sensitization of spinal nociception, and chronic pain risk
Abstract
Adverse life events: A definition
Adverse life events and health
Adverse life events and chronic pain
The impact of adversity (stress) on nociception in animals
Pain systems and their assessment in humans
Adversity and pain processing in humans
Adversity, latent sensitization, and pain risk
Implications and future directions
Summary
Applications to other areas
Other agents of interest
Mini-dictionary of terms
Key facts about adversity
Summary points
Chapter 33: Cognitive-affective modulation of pain: The placebo and nocebo phenomena and their impact on pain treatment
Abstract
Introduction
Psychological mechanisms of placebo analgesia and nocebo hyperalgesia
Neurobiological and neurochemical mechanisms of placebo analgesia and nocebo hyperalgesia
The relevance of placebo and nocebo effects for pain treatment in clinical practice
Applications to other areas
Other agents of interest
Mini-dictionary of terms
Key facts of placebo analgesia
Key facts of nocebo hyperalgesia
Summary points
Chapter 34: Nociception-related behavioral phenotypes in adult zebrafish
Abstract
Introduction
Nociception and pain in animal models
Zebrafish as animal model for translational pain research
Zebrafish-based pain models
Applications to other areas
Other agents of interest
Mini-dictionary of terms
Key facts
Summary points
Chapter 35: Pain, implantable pain devices, and psychosocial aspects of pain
Abstract
Anatomy of pain pathways
Psychosocial aspects of neuropathic pain
Rationale for psychosocial evaluations
Effect of spinal cord stimulation on pain processing
Effects of modes of stimulation on psychosocial aspects of pain
Conclusions
Application to other areas
Other agents of interest
Mini-dictionary of terms
Key facts of pain, implantable devices, and psychosocial aspects of pain
Summary points
Chapter 36: Influence of psychological factors on myofascial pain
Abstract
Introduction
Application to other areas
Other agents of interest
Mini-dictionary of terms
Key facts of myofascial pain
Summary points
Part IV: Resources
Chapter 37: Recommended resources, sites, and research groups for the neuroscience of anesthetics and analgesics
Abstract
Acknowledgments
Introduction
Resources
Applications to other areas
Mini-dictionary of terms
Key points
Summary points
Index

Rajkumar Rajendram

Dr Rajkumar Rajendram is a clinician scientist with a focus on internal medicine, anaesthesia, intensive care and peri-operative medicine. He graduated with distinctions from Guy’s, King’s and St. Thomas Medical School, King’s College London in 2001. As an undergraduate he was awarded several prizes, merits and distinctions in pre-clinical and clinical subjects.

Dr Rajendram began his post-graduate medical training in general medicine and intensive care in Oxford. He attained membership of the Royal College of Physicians (MRCP) in 2004 and completed specialist training in acute and general medicine in Oxford in 2010. Dr Rajendram subsequently practiced as a Consultant in Acute General Medicine at the John Radcliffe Hospital, Oxford.

Dr Rajendram also trained in anaesthesia and intensive care in London and was awarded a fellowship of the Royal College of Anaesthetists (FRCA) in 2009. He completed advanced training in regional anaesthesia and intensive care. He was awarded a fellowship of the Faculty of Intensive Care Medicine (FFICM) in 2013 and obtained the European diploma of intensive care medicine (EDIC) in 2014. He then moved to the Royal Free London Hospitals as a Consultant in Intensive Care, Anaesthesia and Peri-operative Medicine. He has been a fellow of the Royal College of Physicians of Edinburgh (FRCP Edin) and the Royal College of Physicians of London (FRCP Lond) since 2017 and 2019 respectively. He is currently a Consultant in Internal Medicine at King Abdulaziz Medical City, National Guard Heath Affairs, Riyadh, Saudi Arabia.

Dr Rajendram’s focus on improving outcomes from Coronavirus Disease 2019 (COVID-19) has involved research on point of care ultrasound and phenotypes of COVID-19. Dr Rajendram also recognises that nutritional support is a fundamental aspect of medical care. This is particularly important for patients with COVID-19. As a clinician scientist he has therefore devoted significant time and effort into nutritional science research and education. He is an affiliated member of the Nutritional Sciences Research Division of King’s College London and has published over 400 textbook chapters, review articles, peer-reviewed papers and abstracts.

Affiliations and expertise

Consultant in Internal Medicine, King Abdulaziz Medical City, National Guard Heath Affairs, Riyadh, Saudi Arabia

Victor R Preedy

Victor R. Preedy BSc, PhD, DSc, FRSB, FRSPH, FRSC, FRCPath graduated with an Honours Degree in Biology and Physiology with Pharmacology. After gaining his University of London PhD, he received his Membership of the Royal College of Pathologists. He was later awarded his second doctorate (DSc), for his contribution to protein metabolism in health and disease. He is Professor of Clinical Biochemistry (Hon) at King’s College Hospital and Emeritus Professor of Nutritional Biochemistry at King’s College London. He has Honorary Professorships at the University of Hull, and the University of Suffolk. Professor Preedy was the Founding Director and then long-term Director of the Genomics Centre at King’s College London from 2006 to 2020. Professor Preedy has been awarded fellowships of the Royal Society of Biology, the Royal College of Pathologists, the Royal Society for the Promotion of Health, the Royal Institute of Public Health, the Royal Society for Public Health, the Royal Society of Chemistry and the Royal Society of Medicine. He carried out research when attached to the National Heart Hospital (part of Imperial College London), The School of Pharmacy (now part of University College London) and the MRC Centre at Northwick Park Hospital. He has collaborated with international research groups in Finland, Japan, Australia, USA, and Germany. To his credit, Professor Preedy has published over 750 articles, which includes peer-reviewed manuscripts based on original research, abstracts and symposium presentations, reviews and edited books.

Affiliations and expertise

Professor, Department of Clinical Biochemistry, King’s College Hospital, London, UK; Emeritus Professor, Faculty of Life Sciences and Medicine, King’s College London, UK Visiting Professor, University of Hull, UK

Vinood Patel

Vinood B. Patel, BSc, PhD, FRSC, is currently Professor in Clinical Biochemistry at the University of Westminster. In 2014 Dr Patel was elected as a Fellow to The Royal Society of Chemistry. Dr Patel graduated from the University of Portsmouth with a degree in Pharmacology and completed his PhD in protein metabolism from King’s College London in 1997. His postdoctoral work was carried out at Wake Forest University Baptist Medical School, NC, USA studying structural-functional alterations to mitochondrial ribosomes, where he developed novel techniques to characterize their biophysical properties. Research is being undertaken to study the role of nutrients, antioxidants, phytochemicals, iron, alcohol and fatty acids in the pathophysiology of liver disease. Other areas of interest are identifying new biomarkers that can be used for the diagnosis and prognosis of disease and understanding mitochondrial oxidative stress in neurological disorders and iron dysregulation in diabetes. Dr Patel is a nationally and internationally recognized researcher and has several edited biomedical books related to the use or investigation of active agents or components. These books include The Handbook of Nutrition, Diet, and Epigenetics, Branched Chain Amino Acids in Clinical Nutrition, Cancer: Oxidative Stress and Dietary Antioxidants, Toxicology: Oxidative Stress and Dietary Antioxidants, Molecular Nutrition: Vitamins, The Neuroscience of Pain, Cognitive Behavioural Therapy. He is Editor of the ten-volume series Biomarkers in Disease: Methods, Discoveries and Applications.

Affiliations and expertise

Reader, Clinical Biochemistry, University of Westminster, London, UK

Colin R Martin

Colin R. Martin RN, BSc, MSc, PhD, MBA, YCAP, FHEA, C.Psychol, AFBPsS, C.Sci is Professor of Clinical Psychobiology and Applied Psychoneuroimmunology and Clinical Director of the Institute of Health and Wellbeing at the University of Suffolk, UK. He is a Chartered Health Psychologist and a Chartered Scientist. He also trained in analytical biochemistry, this aspect reflecting the psychobiological focus of much of his research within mental health. He has published or has in press well over 300 research papers and book chapters. He is a keen book author and editor having written and/or edited more than 50 books. These outputs include the prophetic insight into the treatment of neurological disease, Handbook of Behavior, Food and Nutrition (2011), Nanomedicine and the Nervous System (2012), Oxidative Stress and Dietary Antioxidants in Neurological Disease (2020), Zika Virus Impact, Diagnosis, Control and Models (2021), Factors Affecting Neurodevelopment: Genetics, Neurology, Behavior and Diet (2021), Diagnosis and Treatment of Spinal Cord Injury (2022), The Neurobiology, Physiology, and Psychology of Pain (2022) and The Handbook of Lifespan Cognitive Behavioral Therapy: Childhood, Adolescence, Pregnancy, Adulthood, and Aging (2023). Professor Martin is particularly interested in all aspects of the relationship between underlying physiological substrates and behavior, particularly in how these relationships manifest in both acute and chronic psychiatric disorder. He has published original research germane to significant mental health disorders including the areas of schizophrenia, anxiety, depression, self-esteem, alcohol and drug dependency, high secure forensic mental health and personality disorder. He has a keen interest in the impact of postviral illness and is actively involved in clinical research post-Covid pandemic and in particular, the impact of Long Covid on psychological, neurological, physiological and social functioning. He is involved in collaborative International research with many European and Non-European countries.

Affiliations and expertise

Professor of Clinical Psychobiology and Applied Psychoneuroimmunology and Clinical Director: Institute for Health and Wellbeing, University of Suffolk, Ipswich, UK

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The Neurobiology, Physiology, and Psychology of Pain

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Rajkumar Rajendram

Victor R Preedy

Vinood Patel

Colin R Martin