Contents

Cure Arthritis Naturally

Cure Arthritis Naturally

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Preface xiii

Acknowledgments xv

Contributors xvii

Part I General Concepts 1

1. Bidirectional Communication Between the Brain and the Immune

System 3

Douglas A. Weigent and J. Edwin Blalock

1.1 Introduction 3

1.2 Nervous System Communication to the Immune System 6

1.3 Neuroendocrine Hormone Influence on the Immune System 8

1.4 Actions of Hypothalamic Releasing Hormones 10

1.5 Immune System Communication with the Nervous System

Hormones 11

1.6 Cytokine Influences on the Nervous System 12

1.7 Neuroendocrine Hormone Release by Cells of the Immune System 14

1.8 Neurotransmitter Release by Cells of the Immune System 16

1.9 Bidirectional Communication and Sleep 17

1.10 Summary and Conclusions 17

2. Neuroimmunological Correlates of Circadian Rhythmicity in Oral Biology and Medicine 27

Francesco Chiappelli, Olivia S. Cajulis, Audrey Navarro and David R. Moradi

2.1 Introduction 27

2.2 Allostatic Response and Allostatic Intervention: Relevance to Oral Biology and Medicine 29

2.2.1 Allostasis 29

2.2.2 Allostatic Load 30

2.2.3 Allostatic Testing and Intervention 32

2.3 Mucositis: A Case of Allostatic Load 36

2.3.1 Oral Mucositis 36

2.3.2 Neuroendocrine-Immune Orderly Chaos in OM 39

2.3.3 Circadian Neurobiology and Neuroimmunopathology in

OM 46

2.4 Directions for the Future 49

3. Circadian Organization of the Immune Response: Lessons from the Adjuvant Arthritis Model 59

Daniel P. Cardinali, Ana I. Esquifino, Georges J. M. Maestroni and Seithikurippu R. Pandi-Perumal

3.1 The Circadian Clock is One of the most Indispensable Biological Functions 59

3.2 The Immune System Shows Circadian Organization 61

3.3 "Sickness Behavior" Includes Changes in Circadian Rhythms 64

3.4 The Rat Adjuvant Arthritis is an Experimental Model of

Rheumatoid Arthritis 66

3.5 Adjuvant Arthritis Disrupts Normal Chronobiological

Organization 68

3.6 Melatonin as a Circadian Immunoregulatory Signal in Adjuvant

Arthritis 72

Part II Basic Research 85

4. The Biological Clock in Inflammation and Sleep Switch Alterations 87

Marina Bentivoglio, Mikael Nygârd, Maria Palomba and Krister Kristensson

4.1 Introduction 87

4.2 Interactions Between the Biological Clock and the Sleep Switch 87

4.3 Effects of Inflammatory Molecules on the SCN and Sleep Switch Structures 90

4.4 Intracellular Inflammatory Regulators 92

4.4.2 Intracellular Regulation of Inflammation and the

Biological Clock 92

4.5 Concluding Remarks 94

5. Vasoactive Intestinal Polypeptide and Prolactin Cytokines: Role in

Sleep and Some Immune Aspects 97

Fabio Garcia-Garcia, Tatiana Olivares-Banuelos and René DruckerColin

5.1 Introduction 97

5.2 Vasoactive Intestinal Polypeptide (VIP) 98

5.2.1 Receptors 98

5.2.2 Gene Regulation 98

5.3 VIP: Brain Distribution 99

5.4 VIP and Sleep Regulation 99

5.5 How VIP Induces REMS: a Hypothesis 102

5.6 VIP Clinical Implications 102

5.7 Prolactin (PRL) 103

5.8 PRL Molecular Aspects 103

5.8.1 Gene Regulation 104

5.8.2 Posttranslational Modifications 104

5.9 PRL and Sleep Regulation 105

5.10 Relationship Between PRL and Stress 107

5.11 Stress and REMS: Role of PRL 108

5.12 PRL Expression and REMS 109

5.13 PRL Clinical Implications 109

6. Immune Signaling to Brain: Mechanisms and Potential Pathways Influencing Sleep 119

Lisa Goehler and Ronald Gaykema

6.1 Introduction 119

6.2 Mechanisms of Immune Signaling to the Brain 119

6.2.1 Neural Pathways 119

6.2.2 Endocrine-Like Pathways: Immune Sensing within the

Brain 122

6.3 Neurocircuitry Mediating Sleep and Waking States 124

6.4 What are the Links Between Immune-Brain Interfaces and Sleep Neurocircuitry? 124

6.4.1 Primary Sensory Relay Nuclei 126

6.4.2 Ascending Pathways Influencing Arousal 127

6.5 Conclusions and Perspectives 127

7. Aging, Sleep, and Immunity 133

Laura-Yvette Gorczynski, Ender Terzioglu, Thierry Waelli and R.M. Gorczynski

7.1 Introduction 133

7.2 Altered Sleep and Concomitant Alterations in Immune Function 133

7.3 Cytokines and Sleep 135

7.4 Relationship of Infection to Altered Sleep Behavior 138

7.5 Stress, Hormonal Change, Cytokines, and Sleep Behavior 140

7.6 Age-Related Changes in Sleep and Relation to Altered Immunity 143

7.7 Summary and Conclusions 148

8. Cytokines and Sleep: Neuro-immune Interactions and Regulations 155

Tetsuya Kushikata, Hitoshi Yoshida and Tadanobu Yasuda

8.1 Introduction 155

8.2 Effect of Sleep on Immune System 155

8.2.1 Sleep Pattern and Immune Function 155

8.2.2 Sleep Deprivation and Immune System 156

8.3 Effect of Modulation of Immune System on Sleep 156

8.3.1 Overview 156

8.3.2 Microbial Products, Cytokines, Sleep 157

8.3.3 Proinflammatory Cytokines on Sleep 157

8.3.4 Anti-Inflammatory Cytokines on Sleep 160

8.3.5 Molecular Level Modulation of Cytokines on Sleep 160

8.4 Conclusion 161

9. Selective REM Sleep Deprivation and Its Impact on the Immune Response 167

Javier Velazquez Moctezuma, José Ángel Rojas Zamorano, Enrique Esqueda León, Andrés Quintanar Stephano and Anabel Jiménez Anguiano

9.1 Introduction 167

9.2 Human Studies 168

9.3 Animal Studies 169

Part III Clinical Research 175

10. Sleep and Immune Correlates: Translational Research in Clinical Populations 177

Sarosh J. Motivala and Michael Irwin

10.1 The Rationale for Studying Sleep and Immunity in Clinical Populations 177

10.2 Sleep and Immunity in Primary Insomnia 178

10.2.1 Effects of Experimental Sleep Loss 178

10.2.2 Primary Insomnia 179

10.2.3 Insomnia in Aging: Influence on Immunity 180

10.2.4 Cytokines: Role in the Regulation of Sleep 181

10.3 Sleep and Immunity in Depression and Substance Dependence 182

10.3.1 Depression and Immunity 183

10.3.2 Alcohol Dependence, Sleep, and Immunity 184

10.4 Sleep and Cytokines in Rheumatoid Arthritis 187

10.5 Future Directions 189

11. The Stress of Inadequate Sleep and Immune Consequences 195

Beatriz Duarte Palma, Sergio Tufik and Deborah Suchecki

11.1 Introduction 195

11.2 Inadequate Sleep and Disease 197

11.3 Immune Function in Sleep Disorders 198

11.4 Hospitalized Patients 199

11.5 Chronic Inflammatory Diseases and Sleep 200

11.6 Concluding remarks 202

12. Neuroimmunology of Pregnancy-Related Sleep Disturbances 207

Michele L. Okun and Mary E. Coussons-Read

12.1 Introduction 207

12.2 Pregnancy and Alterations in Sleep 207

12.2.1 Generalized Sleep Patterns across Pregnancy 207

12.2.2 Sleep Measured by In-lab Polysomnography 208

12.2.3 Sleep Measured by Ambulatory PSG 209

12.2.4 Sleep Measured by Subjective Reports 210

12.3 Understanding Sleep in Pregnancy via Animal Models 212

12.4 Factors That May Contribute to Disrupted Sleep During Pregnancy 212

12.4.1 Psychosocial Factors 212

12.4.2 Immunological Factors—Cytokines 214

12.4.3 Endocrinological Factors—Hormones 215

12.5 Where Does Sleep Fit In? The Cytokine and Hormone Changes Associated with Sleep Deprivation/Sleep Disorders 216

12.6 Pregnancy Complications 218

12.7 Summary 220

13. Changes in Sleep and Behavior Following Experimental Immune Stimulation Using Bacterial Endotoxin in Humans 227

Andreas Schuld, Monika Haack, Janet Mullington, and Thomas Pollmacher

13.1 Introduction 227

13.2 The Role of the Neuroendocrine-Immune-CNS Interplay in

Clinical Medicine 228

13.3 Changes in Sleep-Wake Behavior Following Endotoxin 229

13.4 Changes in Memory, Mood, and Food Intake Following Endotoxin 230

14. Inflammation and Sleep 233

Rita A. Trammell, Krishna Jhaveri, and Linda A. Toth

14.1 Inflammation 233

14.2 Cytokines and Sleep 234

14.3 Acute Inflammation and Sleep 234

14.4 Chronic Inflammation and Sleep 236

14.4.1 Chronic infections 236

14.4.2 Chronic Fatigue Syndrome 237

14.4.3 Obesity and Type-2 Diabetes 238

14.4.4 Cancer 239

14.4.5 Age-Related Inflammation 240

14.5 Genetic Variation in Sleep and Inflammation 240

14.5.1 Genetic Variation in the Inflammatory Response 240

14.5.2 Genetic Variation in Sleep Under Normal Conditions and during Inflammatory Disease 241

14.5.3 The Intersection of Genetic Variation in Sleep and Inflammation 243

14.6 Summary and Conclusions 245

15. Neuroimmune Activation in Sleep Apnea 257

Paul J. Mills, Michael G. Ziegler, and Joel E. Dimsdale

15.1 Introduction 257

15.2 Adrenergic Agonists and Receptors 257

15.3 Norepinephrine Release and Clearance 261

15.4 Cytokines in OSA 263

15.4.1 Cytokines and Normal Sleep 263

15.4.2 Cytokines and OSA 263

15.4.3 What Features of OSA Might Lead to Elevations of Inflammatory Cytokines? 264

15.4.4 Cytokines in the Context of Mood and Quality Of Life in

OSA 265

15.5 Nasal Continuous Positive Airway Pressure 266

15.5.1 CPAP Effects on NE levels and Adrenergic Receptors 267

15.5.2 CPAP Effects on NE Kinetics 269

15.5.3 CPAP Effects on Inflammation 271

15.6 Summary 271

16. Role and Circadian Rhythms of Proinflammatory Cytokines, Cortisol, and Melatonin in Children with Obstructive Sleep Apnea Syndrome 275

Luana Nosetti and Luigi Nespoli

16.1 Obstructive Sleep Apnea Syndrome in Children: Clinical Features 275

16.2 Pathophysiology of OSAS 276

16.3 OSAS Neuroimmunology 277

16.4 Melatonin Role and Circadian Rhythms in Children with OSAS 278

16.5 Cortisol Role and Circadian Rhythms in OSAS 280

16.6 Proinflammatory Cytokines Role and Circadian Rhythms in OSAS 281

16.6.2 Other Cytokines 281

16.6.3 Proinflammatory Cytokines Circadian Rhythms in OSAS 282

17. Neuroendocrine-Immune Correlates of Sleep and Traumatic Brain

Injury (TBI) 285

Paolo Prolo and Anna N. Taylor

17.1 Introduction 285

17.2 TBI and the Neuroendocrine System 285

17.3 TBI and Immune Surveillance 288

17.4 TBI and Sleep 288

17.5 Conclusions 291

18. Neuroimmune Correlates of Sleep in Depression: Role of Cytokines 295

J. Szelenyi and E.S. Vizi

18.1 Introduction 295

18.2 Cytokines and the CNS 295

18.2.1 Cross Talk Between the Innate Immune Response and Sleep 295

18.3 Administering Different Types and Dosages of Cytokines and

Their Effects on Sleep 298

18.4 Effect of Deprivation of Cytokines on the Duration and Pattern of

Sleep 299

18.5 Studying the Effects of Sleep Deprivation/Disruption on Cytokine Production 300

18.6 Regulation of Cytokine Balance by Monoamines in Healthy and in Depressed States 301

18.7 Sleep Disturbances in Diseased States Associated with Altered

Cytokine Profile 304

18.7.1 Infection 304

18.7.2 Depression 305

18.8 Cytokine Balance and Antidepressants 308

18.8.1 Effect of Multitarget Drugs (e.g. Monoamine Transporter

Blockers) 308

18.9 Conclusions 311

19. Sleep and Neuroimmune Function in Chronic Fatigue Syndrome 321

Fumiharu Togo, Benjamin H. Natelson, and Neil Cherniack

19.1 Introduction 321

19.2 Neurological and Neuropsychological Dysfunction in CFS 322

19.3 Sleep Studies in CFS 323

19.4 The Neural Immune System in CFS 327

20. Narcolepsy with Cataplexy. Hypocretin and Immunological Aspects 337

Yves Dauvilliers

20.1 Epidemiology and Clinical Features 337

20.1.1 Excessive Daytime Sleepiness 338

20.1.2 Cataplexy 338

20.1.3 Associated Features 338

20.1.4 Diagnostic Criteria 339

20.2 Pathophysiology 339

20.2.1 Hypocretin (Orexin) System 339

20.2.2 Genetic and Environmental Factors in Human Narcolepsy 343

20.2.3 Autoimmunity Hypothesis in Human Narcolepsy 345

20.3 Treatment 347

20.4 Conclusion 349

Index 353

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Arthritis Joint Pain

Arthritis Joint Pain

Arthritis is a general term which is commonly associated with a number of painful conditions affecting the joints and bones. The term arthritis literally translates to joint inflammation.

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