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 NUTRITIONAL
MODULATORS OF
PAIN IN THE AGING
POPULATION
Page left intentionally blank
 NUTRITIONAL
MODULATORS OF
PAIN IN THE AGING
POPULATION
Edited by
Ronald Ross Watson
University of Arizona, Tucson, AZ, United States

Sherma Zibadi
University of South Florida Medical School, Tampa, FL, United States
Academic Press is an imprint of Elsevier
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 Contents

Contributors xi Specific Types of Diets 26

Preface xiii Polyamine-Reduced Diet 26
Fasting and Dietary Restriction 26
Acknowledgments xv Glossary 27
References 27

A 3. Migraine: Burden of Disease, Treatment,

OVERVIEW OF PAIN: and Prevention
MECHANISMS OF CAUSATION N.N. BRAY, H. KATZ

AND TREATMENT BY FOODS Introduction 35

Clinical Presentation of Migraine 35
Prevalence and Disease Burden 37
1. Overview of Pain in Livestock: Mechanism to Pathophysiology of Migraines 37
Nutritional Control Triggers of Migraines 38
G.S. SENGAR, R. DEB, S. CHAKRABORTY, K. MONDAL, B. VENKATASAN, Diet 38
U. SINGH Environment 39
Other 39
Introduction 3 Migraine Therapy 39
Acute Pain 3 Lifestyle Modifications 39
Chronic Pain 4 Acute Abortive Therapy 39
Nutritional Cure 4 Prophylactic Therapy 40
Minerals and Vitamins in the Cure of Pain 5 The Role of Onabotulinum Toxin a in Migraine Therapy 41
References 6 The Role of Supplements in Migraine Therapy 41
The Role of Behavioral Therapy in Migraine Therapy 43
2. Nutritional Modulators in Chemotherapy-Induced The Role of Alternative Therapies in Migraine Therapy 43
Neuropathic Pain The Role of Diet in Migraine Therapy 43
T. ALEXA-STRATULAT, A. LUCA, M. BĂDESCU, C.-R. BOHOTIN, I.D. ALEXA Conclusions 44
References 44
Introduction 9
Epidemiology 9 4. Myelinodegeneration and Its Influence on Pain:
Signs and Symptoms 9 Aging, Diets, and Genetic Dysregulation
Treatment 10
J. CHEN, S.-M. GUAN
Physiopathology of CIPN 11
Taxanes 11 Introduction 47
Platinum Compounds 12 Age-Related White Matter Changes in the Nervous
Vinca Alkaloids 13 System and Their Relationships with Decline of
Proteasome Inhibitors 13 Various Functional Abilities in Normal Elderly People 49
Vitamins and CIPN 13 Lifespan Trajectory of Myelin Integrity and Myelin
Vitamin E 13 Breakdown Model of AD and Neuropsychiatric Disorders 51
Vitamin A and Related Compounds 15 Age-Related Degenerative Changes in Myelin
B Vitamins 16 and Nerve Fibers in Monkey CNS 52
Nutritional Supplements 17 Lifespan Changes in Myelin Structures of Rat
Acetyl-l-Carnitine 17 Nervous System 53
Omega-3 Fatty Acids 19 Grade-Based Classification of Myelinopathology 55
Alpha-Lipoic Acid 19 Diets as Risk Factors of Myelinopathy
Glutathione 20 and Myelinodegeneration 56
Glutamate and Glutamine 22 Association of Myelinodegeneration with Pain 56
Minerals and Trace Elements 23 Genetic and Molecular Basis of Age-Related
Ca and Mg Infusions 23 Myelinodegeneration 59
Selenium 24 References 62
Lithium 25

v
vi Contents

B 9. Capsicum: A Natural Pain Modulator

Y.A. KULKARNI, S.V. SURYAVANSHI, S.T. AUTI, A.B. GAIKWAD
HERBS AND EXTRACTS
Introduction 107
IN PAIN MANAGEMENT Types of Pain 107
Nociception and Nociceptors 108
5. Getting to the Root of Chronic Inflammation: Response of Nociceptors to Noxious Stimuli 109
Ginger’s Antiinflammatory Properties Pain Modulation 110
Herbal Drugs in Pain Modulation 110
P. INSERRA, A. BROOKS
Genus Capsicum 110
Introduction 67 Chemical Constituents in Capsicum 111
Arthritis 67 Capsicum and Traditional Uses 111
Diabetes Mellitus 68 Capsaicin and Pain Modulation 111
Dysmenorrhea 69 TRPV (Capsaicin) Receptors 113
Cancer 70 Capsaicin Receptors and Pain 113
Respiratory 71 Capsicum and Pain Therapeutics 114
Conclusions 72 Acute and Chronic Pain 114
References 72 Neuropathic Pain 114
Musculoskeletal Pain 115
Osteoarthritic Pain 115
6. Illegal Adulterations of (Traditional) Cancer Pain 115
Herbal Medicines and Dietary Supplements Gastric Pain 116
for the Treatment of Pain Pruritus 116
E. DECONINCK Marketed Formulations 116
Summary 116
Introduction 75 List of Abbreviations 117
Counterfeiting and Confounding References 117
of Herbal Treatments 76
Chemical Adulterations of Herbal Treatments 77
Pharmacology of Most Encountered Chemical Adulterants
for the Treatment of Pain 78
C
Analytical Challenges and Solutions 80 ROLE OF PAIN: DIET, FOOD
Conclusions 82
References 83
AND NUTRITION IN PREVENTION
AND TREATMENT
7. Diabetic Neuropathy Modulation by Zinc and/or
Polyphenol Administration 10. Honey—A Natural Remedy for Pain Relief
L. BĂDESCU, M. CIOCOIU, C. BĂDESCU, M. BĂDESCU N.M. LAZIM, A. BAHARUDIN

Introduction 87 Introduction 123

Rationale for the Research 87 Honey Types and its Components 124
Laboratory Evaluation 89 Specific Properties of Honey 125
Serum Glucose 89 Medicinal Value of Honey 126
Glycosylated Hemoglobin 90 Antibacterial and Antiinflammatory Effects of Honey 126
Stimulus Detection Electrodiagnosis 92 Honey Wound Healing Property 127
Discussions 98 Immunomodulation Effects of Honey 128
Conclusions 98 Antinociceptive Effects of Honey 128
References 99 Pain Relief in Postoperative Patients 128
Pain Relief in Radiation Induced Mucositis 130
8. Natural Remedies for Treatment of Cancer Pain Mechanisms of Pain Relief 130
Conclusions 132
M.S. GARUD, M.J. OZA, A.B. GAIKWAD, Y.A. KULKARNI
References 132
Introduction 101
Treatment of Cancer Pain with Natural Remedies 102 11. Probiotics and Synbiotics for Management of
Natural Opioids 103 Infantile Colic
Cannabis (Marijuana) 104 H. AHANCHIAN, A. JAVID
Tetrodotoxin 104
Summary 105 Infantile Colic 135
References 105 Gut–Brain Axis and Microbiota 135

  
 Contents vii
Probiotic Definition 136 Regional Anesthesia and Analgesia 174
Probiotics for Reducing Colic and Pain 137 Thoracic Epidural Catheterization in the Obese 175
Conclusions 138 Complementary and Alternative Medicine Therapies 175
References 138 Diets 175
Low Carbohydrate Diet 175
Ketogenic Diet 176
D Perioperative Considerations of Dietary Supplements
Melatonin
176
176
OBESITY AND MACRONUTRIENTS St. John’s Wort (Hypericum perforatum) 177
IN PAIN Gingko Biloba 177
Kava Kava 177
Omega 3 Fish Oil 177
12. The Interrelationship of Obesity, Honokiol 177
Pain, and Diet/Nutrition The Future of Pain- Pharmacogenetic Testing 178
H.M. RODGERS References 178

Overview of Obesity: Etiology and Dietary Behavior 143

Dietary Behavior
Obesity and Pain
143
144
E
Chronic Pain and Obesity 144 NUTRIENTS IN PAIN IN
Altered Pain Thresholds and Obesity 144
Modulators of Pain in Obesity 145
PREVENTION AND TREATMENT
Treatment and Prevention of Pain in Obesity 147
References 148 15. Vitamin D Deficiency in Joint Pain:
Effects of Vitamin D Supplementation
13. Effects of Obesity on Function and Quality B. ANTONY, C. DING
of Life in Chronic Pain
L.I. ARRANZ Introduction 183
Vitamin D Deficiency and Joint Pain 183
Introduction 151 Prevalence of Joint Pain 183
Effects of Obesity on Function and QoL in Chronic Pain Mechanisms Underlying Link Between Vitamin D
Conditions 152 and Joint Pain 183
General Relationship Between Obesity and Pain, Evidence of the Association Between Vitamin D
Quality of Life, and Disability 152 and Joint Pain 185
Effects of Obesity and Chronic Pain Supplementation of Vitamin D for Joint Pain 186
on Function and QoL 153 Vitamin D Supplementation in Osteoarthritis 186
Obesity and Macronutrients in Pain 158 Vitamin D Supplementation in Rheumatoid
Diet, Macronutrients, and Other Related Arthritis 186
Factors Influencing Obesity and Pain 158 Conclusions 187
Conclusions 165 References 188
References 166
16. Nutritional Modulators of Pain in the Aging
14. Postoperative Analgesia in Morbid Obesity: Population
An Overview of Multimodal Analgesia J. SMITHSON, K.A. KELLICK, K. MERGENHAGEN
and Complimentary Therapies
M.M. AMAN, A. MAHMOUD, A.C. SINHA
Background 191
Vitamin D Deficiency 192
Introduction 171 Omega-3 Polyunsaturated Fatty Acids 193
Burden of Morbid Obesity 171 Magnesium 193
Pain in the Obese Patient 172 Willow Bark 194
Obesity and Hormonal Regulation of Acute Pain 172 Probiotics 194
Systemic Opioids in the morbidly Obese 172 Glucosamine and Chondroitin 194
Opioid Pharmacology and Pharmacokinetics Turmeric 195
in the Morbidly Obese 173 Devil’s Claw 195
Opioid Patient Controlled Analgesia 173 Methylsulfonylmethane 195
Multimodal Strategies in the Acute Boswellia 195
Postoperative Phase 173 Green Tea 196
Nonopioid Systemic Analgesics 174 Summary 196
Systemic Adjuvants 174 References 197

  
viii Contents

17. Trace Elements Alleviate Pain 20. Conservative and Postoperative Coanalgesic
in Mice and Humans Therapy for Upper Limb Tendinopathy
B.I. TAMBA, T. ALEXA-STRATULAT Using Dietary Supplements
GIOVANNI MEROLLA, S. CERCIELLO
Introduction 199
Zinc 199 Introduction 235
Theoretical Background 199 Tendon Degeneration, Inflammation, and Pain 236
Fundamental Studies 200 Rationale for the Use of Standard Antiinflammatory Drugs 236
Clinical Studies 201 Antiinflammatory and Analgesic Activity
Magnesium 202 of Dietary Supplements 236
Theoretical Background 202 Clinical Applications of Dietary Supplements to Treat
Fundamental Studies 202 Tendinopathy and Reduce Pain After Tendon Repair Surgery 238
Clinical Studies 203 References 241
Manganese 205
Theoretical Background 205 21. Folic Acid in Pain: An Epigenetic Link
Fundamental Studies 205
N. SHARMA, A.B. GAIKWAD, Y.A. KULKARNI
Clinical Studies 205
Selenium 205 Introduction 245
Theoretical Background 205 Vitamins 246
Fundamental Studies 206 Folic Acid 246
Clinical Studies 206 Epigenetics 246
Copper 207 Folic Acid and DNA Methylation 247
Theoretical Background 207 Folic Acid and Rheumatoid Arthritis 247
Fundamental Studies 207 Role of Folic Acid in Colorectal Adenomas 249
Clinical Studies 207 Role of Folic Acid in Myofascial Pain 249
Strontium 208 List of Abbreviations 249
Introduction 208 References 250
Fundamental Studies 208
Clinical Studies 209
Other Essential and Nonessential
Trace Elements 209
F
Conclusions 211 ANIMAL MODELS FOR PAIN:
References 211 FOOD AND PLANT EXTRACT
18. Vitamin B12 for Relieving Pain
in Aphthous Ulcers 22. Analgesic and Neuroprotective
H.-L. LIU Effects of B Vitamins
X.-J. SONG
Introduction 217
Epidemiology of Aphthous Ulcer 217 Analgesic Effects of B Vitamins on Acute Pain 255
Types of Mouth Ulcer 218 Analgesic Effect of B Vitamins on Painful
Cause of Canker Sores 218 Diabetic Neuropathy 256
Aphthous Ulcer Treatment 218 Analgesic Effect of B Vitamins on Neuropathic Pain After
Vitamin B12 Treatment for Mouth Ulcer 218 Peripheral Nerve Injury and Dorsal Root Ganglion
Treatment for Pain in Apththous Ulcers 219 Compression 257
References 221 Analgesic and Neuroprotective Effects of B Vitamins
Following Temporary Spinal Cord Ischemia 258
19. Vitamin K, Osteoarthritis, and Joint Pain Mechanisms Underlying Analgesic Effects of B Vitamins 259
References 261
M.K. SHEA, S.L. BOOTH

Vitamin K Sources 225 23. Pain Relief in Chronic Pancreatitis—Role of

Vitamin K and Osteoarthritis: Underlying Mechanisms 226 Nutritional Antioxidants
Biomarkers of Vitamin K Status Used in Osteoarthritis P. BHARDWAJ, R.K. YADAV, P.K. GARG
Studies 227
Vitamin K and Osteoarthritis: Evidence From Human Introduction 265
Studies 228 Free Radicals in Cellular Physiology and Pathophysiology 265
Conclusions and Future Directions 230 Endogenous Sources of Free Radicals 266
References 231 Exogenous Sources of Free Radicals 266

  
 Contents ix
Free Radicals in Pancreatic Pathophysiology 266 25. Review of Fortified Foods and Natural
Sources of Free Radicals in Pancreas 266 Medicinal Products in Companion Animals
Oxidative Stress and Inflammation in Pancreas 267
Pain in Chronic Pancreatitis 267
Afflicted by Naturally Occurring Osteoarthritis
Antioxidant Defense in Cellular Physiology 268 M. MOREAU, E. TRONCY

Nutritional Antioxidants 268

Introduction 281
Vitamin C 268
Clinical Trial Objective and Purposes 282
Vitamin E 269
Design and Recruitment 283
Carotenoids and Vitamin A 269
Outcomes 283
Methionine 269
Control and Tested Substances 284
Selenium 269
Blinding and Randomization 284
Dietary Antioxidants as Modulators of Pain
Data Analysis 285
and Oxidative Stress 269
Critical Analysis 285
Way Forward 270
Positioning of Fortified Foods and Natural
References 270
Medicinal Products 288
Concluding Remarks and Future Recommendations 288
24. Vitamin D and Disc Herniation References 289
Associated Pain
M. SEDIGHI
Index 293
Dedication 277
References 277

  
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 Contributors

H. Ahanchian Children’s Health and Environment Program, A. Brooks Virginia State University College of Agriculture,
Queensland Children’s Medical Research Institute, Petersburg, VA, United States
University of Queensland, Brisbane, QLD, Australia; S. Cerciello Casa di cura Villa Betania, Rome; Marrelli
Department of Allergy and Immunology, Mashhad Hospital, Crotone, Italy
University of Medical Sciences, Mashhad, Iran
S. Chakraborty Animal Resources Development
I.D. Alexa Centre for the Study and Therapy of Pain, Grigore Department, Agartala, Tripura, India
T. Popa University of Medicine and Pharmacy, Iasi, Romania
J. Chen Institute for Biomedical Sciences of Pain, Tangdu
T. Alexa-Stratulat Centre for the Study and Therapy of Pain, Hospital, The Fourth Military Medical University, Xi’an;
Grigore T. Popa University of Medicine and Pharmacy, Iasi, Key Laboratory of Brain Stress and Behavior, PLA, Xi’an;
Romania Beijing Institute for Brain Disorders, Beijing, People’s
M.M. Aman Department of Anesthesiology, Drexel University Republic of China
College of Medicine, Philadelphia, PA, United States M. Ciocoiu Department of Pathophysiology, St. Spiridon
B. Antony Menzies Institute for Medical Research, Hospital, University of Medicine and Pharmacy “Grigore T.
University of Tasmania, Hobart, TAS, Australia Popa”, Iasi, Romania
L.I. Arranz Department of Nutrition and Food Sciences, R. Deb ICAR, Central Institute for Research on Cattle,
Faculty of Pharmacy, University of Barcelona, Barcelona, Meerut, Uttar Pradesh, India
Spain E. Deconinck Division of Food, Medicines and Consumer
S.T. Awati Shobhaben Pratapbhai Patel School of Pharmacy Safety, Section Medicinal Products, Scientific Institute of
& Technology Management, SVKM’s NMIMS, Vile Parle Public Health (WIV-ISP), Brussels, Belgium
(West), Mumbai, Maharashtra, India C. Ding Menzies Institute for Medical Research,
C. Bădescu Internal Medicine Clinic, St. Spiridon Hospital, University of Tasmania, Hobart, TAS, Australia;
University of Medicine and Pharmacy “Grigore T. Popa”, Translational Research Centre, Academy of Orthopaedics,
Iasi, Romania Southern Medical University, Guangzhou, Guangdong
L. Bădescu Department of Cell and Molecular Biology, Province, China
St. Spiridon Hospital, University of Medicine and A.B. Gaikwad Department of Pharmacy, Birla Institute
Pharmacy “Grigore T. Popa”, Iasi, Romania of Technology and Science, Pilani Campus, Pilani,
M. Bădescu Department of Pathophysiology, St. Spiridon Rajasthan, India
Hospital, University of Medicine and Pharmacy P.K. Garg Department of Gastroenterology, All India
“Grigore T. Popa”, Iasi, Romania Institute of Medical Sciences, New Delhi, India
A. Baharudin Department of Otorhinolaryngology, Head M.S. Garud Shobhaben Pratapbhai Patel School of
and Neck Surgery, School of Medical Sciences, Universiti Pharmacy & Technology Management, SVKM’s NMIMS,
Sains Malaysia, Kubang Kerian, Kelantan, Malaysia Mumbai, Maharashtra, India
A. Bhanudas Gaikwad Department of Pharmacy, Birla S.-M. Guan School of Stomatology, The Fourth Military
Institute of Technology and Science, Pilani Campus, Pilani, Medical University, Xi’an, People’s Republic of China
Rajasthan, India P. Inserra John Tyler Community College, Chester, VA,
P. Bhardwaj Department of Gastroenterology, All India United States
Institute of Medical Sciences, New Delhi; Tata Consultancy A. Javid Department of Pediatrics, Mashhad University of
Services, Noida, Uttar Pradesh, India Medical Science, Mashhad, Iran
C.-R. Bohotin Centre for the Study and Therapy of Pain, H. Katz Broward Health Medical Center, Fort Lauderdale,
University of Medicine and Pharmacy Gr. T. Popa, Iasi, FL, United States
Romania
K.A. Kellick VA Western New York Healthcare System,
S.L. Booth Jean Mayer Human Nutrition Research Center Buffalo, NY, United States
on Aging, Tufts University, Boston, MA, United States
Y.A. Kulkarni Shobhaben Pratapbhai Patel School of
N.N. Bray Broward Health Medical Center, Fort Lauderdale, Pharmacy & Technology Management, SVKM’s NMIMS,
FL, United States Vile Parle (West), Mumbai, Maharashtra, India

xi
xii Contributors

N.M. Lazim Department of Otorhinolaryngology, Head and M. Sedighi Shiraz Medical School, Shiraz University of
Neck Surgery, School of Medical Sciences, Universiti Sains Medical Sciences (Shiraz Branch), Shiraz, Iran
Malaysia, Kubang Kerian, Kelantan, Malaysia G. Sengar ICAR, Central Institute for Research on Cattle,
H.-L. Liu Department of Nursing, Central Taiwan Meerut, Uttar Pradesh, India
University of Science and Technology, Beitun District, N. Sharma Department of Pharmacy, Birla Institute of
Taichung City, Taiwan Technology and Science, Pilani Campus, Pilani, Rajasthan,
A. Luca Centre for the Study and Therapy of Pain, India
University of Medicine and Pharmacy Gr. T. Popa, Iasi, M.K. Shea Jean Mayer Human Nutrition Research Center
Romania on Aging, Tufts University, Boston, MA, United States
A. Mahmoud Department of Anesthesiology, John H. U. Singh ICAR, Central Institute for Research on Cattle,
Stroger, Jr. Hospital of Cook County, Chicago, IL, United Meerut, Uttar Pradesh, India
States
A.C. Sinha Department of Anesthesiology, Drexel University
K. Mandal West Bengal Agricultural University, Krishnagar, College of Medicine, Philadelphia, PA, United States
West Bengal, India
J. Smithson VA Western New York Healthcare System,
K. Mergenhagen VA Western New York Healthcare System, Buffalo, NY, United States
Buffalo, NY, United States
X.-J. Song Section of Basic Science Research, Parker
Giovanni Merolla Shoulder and Elbow Surgery University Research Institute, Dallas, TX, United States
Unit, “D. Cervesi” Hospital, Cattolica, AUSL della
S.V. Suryavanshi Shobhaben Pratapbhai Patel School of
Romagna Ambito Territoriale di Rimini, Cattolica
Pharmacy & Technology Management, SVKM’s NMIMS,
Rimini; “Marco Simoncelli” Biomechanics Laboratory,
Vile Parle (West), Mumbai, Maharashtra, India
“D. Cervesi” Hospital, Cattolica, AUSL della Romagna
AmbitoTerritoriale di Rimini, Cattolica, Rimini, Italy B.I. Tamba Centre for the Study and Therapy of Pain,
Grigore T. Popa University of Medicine and Pharmacy, Iasi,
M. Moreau Research Group in Animal Pharmacology of
Romania
Quebec (GREPAQ), Department of Veterinary Biomedical
Sciences, Faculty of Veterinary Medicine, Université de E. Troncy Research Group in Animal Pharmacology of
Montréal, Saint-Hyacinthe, QC; Osteoarthritis Research Quebec (GREPAQ), Department of Veterinary Biomedical
Unit, University of Montreal Hospital Research Centre Sciences, Faculty of Veterinary Medicine, Université de
(CRCHUM), Montreal, QC, Canada Montréal, Saint-Hyacinthe, QC; Osteoarthritis Research
Unit, University of Montreal Hospital Research Centre
M.J. Oza Shobhaben Pratapbhai Patel School of Pharmacy
(CRCHUM), Montreal, QC, Canada
& Technology Management, SVKM’s NMIMS, Vile
Parle (West); SVKM’s Dr. Bhanuben Nanavati College of B. Venkatasan ICAR, Central Institute for Research on
Pharmacy, Mumbai, Maharashtra, India Cattle, Meerut, Uttar Pradesh, India
H.M. Rodgers West Virginia University School of Medicine, R.K. Yadav Department of Physiology, All India Institute of
Morgantown, WV, United States Medical Sciences, New Delhi, India

  
 Preface

Treatment with opioid like painkiller with powerful interactions between obesity and pain and ultimately the
new drugs (OxyContin) is a major cause of their dramat- effects of nutritional changes. Then Arranz Inglesis dis-
ic rise in use and abuse, as well as the related compound, cusses obesity as an adverse promoter of pain, lifestyle,
heroin. This strengthens the already present interest in and physiological functions. Finally, Sinha describes the
alternatives to pain medicines, such as dietary materials, roles of diet and supplements in postoperative analgesia
the focus of this book. after this therapy to reduce morbid obesity. This book
Section A: Overview of Pain: Mechanisms of Causation helps to understand the usefulness and to change the
and Treatment by Foods Pain involves an unpleasant feel- way we think about pain and functional foods and nu-
ing often caused by intense or damaging stimuli. The trition in treatment of chronic pain with less pharmaceu-
International Association for the Study of Pain states: tical drugs. While someday in the not too distant future
“pain is an unpleasant sensory and emotional experi- chronic pain and its causative conditions may be cured
ence associated with actual or potential tissue damage, by genetics or bioengineering, prevention, and treatment
or described in terms of such damage.” Chronic pain with nutrition and lifestyle is critical for reducing health
can persist despite removal of the stimulus and appar- care costs and promoting healthy aging.
ent healing of the body. While most pain is momentary, Section E: Nutrients in Pain in Prevention and Treat-
continuing until the stimulus is removed, chronic pain ment. Ding describes the negative effects in pain pro-
caused by rheumatoid arthritis, peripheral neuropa- duction that comes by vitamin D inadequacy. Nutrient
thy, obesity, cancer, and idiopathic pain can last for a requirements for optimum health and function of ag-
lifetime. Pain is the most common reason for physician ing physiological systems often are quite distinct from
consultation and a major component of many disease those required for young people. Recognition and un-
states. Deb et al. review the mechanisms of pain. Al- derstanding of the special nutrition problems of the
exa’s group describing nutritional modulation of che- aged are being intensively researched and tested, espe-
motherapy induced neuropathic pain. Bray discusses a cially due to the increases in the elderly as a percentage
major pain, migraine. Finally Chen’s group describes of the population. Then Smithson’s group discusses oth-
myelinodegeneration as influenced by age, diet, and er nutrients, which modulate pain in the aging adult.
genetic dysregulation. Tamba and Alexa review nonvitamins, trace elements
Section B: Herbs and Extracts in Pain Management In- in both animal models and humans in pain therapy.
serra and Brooks investigate the uses of ginger via in- Liu reviews a major vitamin, vitamin B12 in the spe-
flammation modulation. There are groups, who do not cific aphthous ulcer induced pain. Shea et al. describe
use the best practices and have adulterations. Deconinck vitamin K, a major supplement in seniors in relieving
reviews illegal adulterations of traditional herbs for pain arthritic pain, osteoarthritis, and joint pain. Cerciello
treatment. Then Bădescu and coauthors describe dia- and Merolla review dietary supplements to limit post-
betic neuropathy, which is difficult to treat and describe operative pain using coanalgesic upper tendoninopa-
zinc and polyphenol’s role. Many chronic diseases and thy. Sharma reviews another vitamin folic acid in pain
cancers are found with higher frequency in the aged. Ga- as an epigenetic link.
rud et al. further discuss cancer pain and natural rem- Section F: Animal Models for Pain: Food and Plant Ex-
edies. Finally capsicum, a natural pain modulation by tracts. Song evaluates the family of B vitamins in neuro-
Kulkarni and coworkers. protection and pain therapy. Bhardwaj et al. review
Section C: Role of Pain: Diet, Food and Nutrition in Pre- nutrients as antioxidants in chronic pain due to pancre-
vention and Treatment Lazim discusses honey, a historic atitis. Many elderly are using foods and nutrients well
therapy for a variety of pain for relief. Not unexpectedly, above the recommended daily allowance, which may
there are many reports of probiotics for pain especially not always be needed for optimal health. The major
in youth by Ahanchian. objective of this book is to review in detail the health
Section D: Obesity and Macronutrients in Pain. Rodgers problems producing or resulting from pain as modified
does an excellent review describing obesity, which plays by functional and normal food, nutrition and dietary
many roles in disease promotion. She describes the supplements to help treat them.

xiii
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 Acknowledgments

The work of Dr. Watson’s editorial assistant, Bethany nonprofit organization that supports science-based re-
L. Stevens, in communicating with authors and work- search on natural health and wellness. It is committed
ing on the manuscripts was critical to the successful to informing about scientific evidence on the useful-
completion of Nutritional Modulators of Pain in the Ag- ness and cost-effectiveness of diet, supplements, and
ing Population. The support of Kathy Padilla, Develop- a healthy lifestyle to improve health and wellness, and
ment Editor, is also very much appreciated. Support reduce disease. Finally, the work of librarian Mari Stod-
for Ms. Stevens’ and Dr. Watson’s work was gracious- dard, of the Arizona Health Science Library, was vital
ly provided by Natural Health Research Institute and very helpful in identifying key researchers who
www.naturalhealthresearch.org. It is an independent, participated in the book.

xv
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 S E C T I O N A

OVERVIEW OF PAIN: MECHANISMS

OF CAUSATION AND TREATMENT
BY FOODS
1 Overview of pain in livestock:
mechanism to nutritional control 3
2 Nutritional modulators in chemotherapy-
induced neuropathic pain 9
3 Migraine: burden of disease, treatment,
and prevention 35
4 Myelinodegeneration and its influence
on pain: aging, diets and genetic
dysregulation 47
Page left intentionally blank
 C H A P T E R

1
Overview of Pain in Livestock:
Mechanism to Nutritional Control
G.S. Sengar*, R. Deb*, S. Chakraborty**,
K. Mondal†, B. Venkatasan*, U. Singh*
*ICAR, Central Institute for Research on Cattle, Meerut, Uttar Pradesh, India; **Animal Resources
Development Department, Agartala, Tripura, India; †West Bengal Agricultural University, Krishnagar,
West Bengal, India

INTRODUCTION the case of lamb. There is no way to directly measure pain

but by investigation of a wide variety of behavioral and
There are certain problems in measuring and evaluat- physiological parameters in response to a noxious event
ing animal welfare and pain and at the same time it is an informed judgment can be made as to whether an ani-
subjective in nature as there is no measurable parameter, mal experiences pain and thereby attempts for minimiz-
which can be specifically indicative of pain. Pain in ani- ing suffering and improving welfare. This chapter deals
mal is aversive sensory, as well as emotional experience with an overview of pain in livestock and mechanism
that represents an awareness of damage or threat to the of cure nutritionally (Alban, Agger, & Lawson, 1996;
tissue integrity by the animal. Therefore, a painful experi- Barnett et al., 1999; Bateson, 1991; Bath, 1998; Calavas,
ence results in changes in physiology, behavioral output, Bugnard, Ducrot, & Sulpice, 1998; Corr, 1999; Cottrell &
which is designed for minimizing or avoiding further Molony, 1995; Danbury, Weeks, Chambers, Waterman-
damage; thereby reducing the likelihood of repeating Pearson, & Kestin, 2000; Duncan, Beaty, Hocking, &
the experience, as well as for ensuring recovery from any Duff, 1991; Fraser & Duncan, 1998).
kind of damage or injury incurred upon. It is not possible
to directly measure subjective experiences or emotions
in case of animals for which measurement of potential- ACUTE PAIN
ly painful stimulus is required. It is required to analyze
information on the normal behavior that is pain free in For a few hours or days, acute or short-term pain lasts
nature for comparing with any abnormal behavior. There and thereby should not outleast the process of healing.
is activation of the sympathetic nervous system due to There is development of acute pain due to many proce-
acute pain thereby changing the heart rate, diameter of dures to which we subject animals to. Such procedures
pupils, tone of the skin, peripheral blood flow, and in re- include mutilations namely, castration, tail docking,
leasing corticosteroids. Analgesics namely, opioids (like disbudding or horn bud destruction, dehorning, brand-
morphine); a2 agonists (like xylazine), and NSAIDs (like ing, debarking, and so also procedures of management
aspirin) have got a minor impact on many procedures namely, shackling, transport, milking, and housing which
but xylazine has been found to actually reduce the physi- can result in acute painful states (Gentle, Hunter, & Corr,
ological and behavioral effects of tail docking. In order 1997; Gentle, Hunter, & Waddington, 1991; Gentle &
to monitor pain in animals recording of electrical activ- Tilston, 2000; Gonyou, 1994; Graf & Senn, 1999; Hassall,
ity from the nervous system is found to be a more direct Ward, & Murray, 1993; Haussmann, Lay, Buchanan,
approach. During castration and docking of tail there is & Hopper, 1999; Hemsworth, Barnett, Beveridge, &
increase in the neural activity significantly, particularly in Matthews, 1995).

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4 1. Overview of Pain in Livestock: Mechanism to Nutritional Control

CHRONIC PAIN of the limb may remain as the sole solution but there
may be problems in the rest of the limbs. Bone grafts
There is increase in the occurrence of long-term pain- have been used for replacement of the damaged tissues,
ful conditions due to intensive farming practiced cur- however, problem with this type of major surgical in-
rently that lasts for weeks to months beyond the time tervention is that the financial cost involvement is more
of expected healing; thereby there is deterioration in to the farmer. So the more efficacious is, the problem
welfare of animals and reduction in production, as well that is prevented or at least if the animal is treated ef-
as financial gain. A collection of diseases is lameness, fectively at an early stage of the disease (Jacobsen, 1996;
a common chronic condition that affects dairy cows, Kent, Jackson, Molony, & Hosie, 2000; Kestin, Knowles,
chickens, and sheep and is a major health problem not Tinch, & Gregory, 1992; Lay, Friend, Grissom, Bowers,
only because of the difficulty in animal in walking but & Mal, 1992; Ley, Livingston, & Waterman, 1991; Ley,
also based on the problems in association with lameness Waterman, Livingston, & Parkinson, 1994; McGeown,
namely, pain, reduction in intake of feed, and loss in Danbury, Waterman-Pearson, & Kestin, 1999; Mc-
body condition. There is pain for long duration substan- Glone, Nicholson, Hellman, & Herzog, 1993; Molony &
tially and also there is increased costs to the farmer due Kent, 1997; Molony, Kent, Fleetwood-Walker, Munro,
to increase in requirement of labor, cost of treatment, & Parker, 1993; Ong et al., 1997; Riley & Farrow, 1998;
reduction in milk production, and fertility, and involun- Rushen, Foxcroft, & DePassille, 1993; Shearer & Her-
tary culling as well as decreased value of slaughter. The nandez, 2000; Schwartzkopf-Genswein & Stookey, 1997;
welfare implications of lameness include reduction in Schwartzkopf-Genswein, Stookey, Crowe, & Gens-
mobility and detrimental effects on physiology and be- wein, 1998; Schwartzkopf-Genswein, Stookey, dePas-
havior that include increase in susceptibility to disease, sille, & Rushen, 1997; Sparrey & Kettlewell, 1994; Thorn-
pain, and discomfort. The cows that are acutely affected ton & Waterman-Pearson, 1999; Weary, Braithwaite,
have got reluctancy in getting up or to move and to walk & Fraser, 1998; Weary & Fraser, 1995; Whay, 1997;
with great tenderness due to pain in the digits. Papil- Wood, Molony, Fleetwood-Walker, Hodgson, & Mel-
lomatous digital dermatitis and laminitis are both major lor, 1991; Yeruham et al., 1999; Zanella, Broom, Hunter,
causes of pain and lameness which cause lesions, foul & Mendl, 1996).
in the foot, there is also separation of sole at the heel,
exudate leakage, necrotic dermatitis, alopecia, and hy-
perkeratosis of the tail. There is also lameness in case of NUTRITIONAL CURE
sheep due to foot rot causing chronic pain and impair-
ing gait that gets reflected in increased level of cortisol The only path to relief of pain may not be pharma-
in plasma that can get elevated for 3 months. In case of ceutical drugs. An increasingly popular way for manag-
broilers and chicken’s meat and turkeys there is lame- ing pain is the natural treatment of pain namely, herbal
ness resulting in pain. It has been found that there is a se- medicines, wherein a part of a plant is used for the treat-
lection of bird’s meat for rapid growth, which results in ment of health problems. Researches on herbal remedies
too heavy weight thereby producing difficulties in carry- are still in its infancy but several herbs are thought to
ing their bodies. This causes distortion of their skeleton. provide management of pain and thereby decrease in-
It has been found through studies that a normal chicken flammation. However, to exercise caution is mandatory.
takes 11 s on an average for walking a set of distance Herbals or other neutraceuticals that may help in cer-
whereas a lame chicken takes 34 s. Especially, in broiler tain ways (and those which may not help actually) have
chickens lameness have been detected to cause abnormal got the potential of harming through side effects that are
gait that becomes detectable in 90% of the birds. Such unwanted with allergic reactions, and undesirable inter-
fast-growing birds have got more muscles in breast and actions with other substances and medicines. The Duke
legs that are shorter and wider with bones which, are im- Integrative Medicine (a division of Duke University
mature. Thereby, leading to a typical short step feet that Medical Center in Durham) has carried out researches
are positioned wide apart and turned out which result in on the basis of which it can be said that, against such
abnormally large mediolateral force that are required to likely effectiveness safety must be very carefully bal-
move to the center of gravity of the bird over the stance anced (Wanzala et al., 2005; Toyang, Wanyama, Nuwan-
leg. Skeletal disease also gives rise to possible pain that yakpa, & Django, 2007; Rigat, Bonet, Garcia, Garnatje, &
has been investigated by use of analgesics with certain Vallés, 2009; Ghosh & Das, 2007; Pieroni, 2010; Kumar,
evidence of pain in association with lameness. Among Vijayakumar, Govindarajan, & Pushpangadan, 2007;
young calves, infectious arthritis and osteomyelitis are Roberts, Black, Santamauro, & Zaloga, 1998; Arun,
common and in case of chronic infectious arthritis, there Satish, & Anima, 2013; Biswas & Mukherjee, 2003; Ti-
may not be effective antibodies since there are difficul- wari, Kumar, Singh, & Gangwar, 2012; Gantwerker &
ties in treating the infections. As a last effort, amputation Hom, 2011).

A. Overview of Pain: Mechanisms of Causation and Treatment by Foods

 Minerals and Vitamins in the Cure of Pain 5
There are certain common herbal remedies that are MINERALS AND VITAMINS
used for natural relief to pain. They are: (1) Capsaicin: IN THE CURE OF PAIN
it is derived from hot chilli peppers. It has been found
that capsaicin topically may be beneficial in certain in- In case of Plantar fasciitis or if there is pain in heel,
stances. It works by depletion of substance P that con- the primary option for healing will revolve around
veys the sensation of pain from the periphery to the rest, icing the heels, doing heel stretching exercises,
central nervous system. (2) Ginger: extracts of ginger and so on. However, one must remember that certain
are helpful in case of joint, as well as muscle pain as it minerals and vitamins also play crucial role in heeling
contains phytochemicals that help in reducing inflam- pain (Abd-Rabou et al., 2012; Hasler, 2005; Hoffman
mation. In small doses if taken, few side effects have & Pfaller, 2001; Hayden & Ghosh, 2008; Hemarajata &
been linked with. (3) Feverfew: for centuries, it has been Versalovic, 2013; Hemilä, Kaprio, Pietinen, Albanes, &
used for treating stomachaches, as well as toothaches. Heinonen, 1999; Hemilä, 2006; Hess & Greenberg, 2012;
It is nowadays used for rheumatoid arthritis. The herb Hesta et al., 2009; Hidiroglou, 1979; Bachiega, Sousa,
is interestingly not associated with any serious side Bastos, & Sforcin, 2012). Such minerals and vitamins are
effects. There are however, mild side effects, such as discussed under the following subheadings:
canker sores, irritation on tongue and lips. (4) Turmeric:
this spice has been used particularly for relieving ar- 1. Calcium:
thritic pain and heartburn and also for reducing inflam- Daily intake of calcium in adequate quantity may
mation. Its activity may be due to a chemical known as help prevent spur development (bony, calcium
curcumin that has got antiinflammatory characteristics. protrusions that are formed on the heel as a result
It is usually safe to use turmeric but it has been found of Plantar fasciitis). A daily calcium supplement
that high doses or long-term use may result in indiges- can be taken or direct inclusion of calcium in the
tion. (5) Devil’s claw: there are certain scientific evidenc- diet may also help. Almonds, sesame seeds, kale,
es that this particular South African herb may become turnip greens, black-eyed peas, and oranges are good
effective for management of arthritis and lower back sources of calcium (Central Institute for Research on
pain but more researches are however, required. There Cattle (ICAR), Meerut, Uttar Pradesh, India).
are rare side effects if used at therapeutic dose that also 2. Magnesium:
for short term but is not advised in case of pregnancy. While calcium is taken in the diet or in the form
There are several other herbal remedies for natural of supplement it must be remembered that certain
relief of pain that include boswellia and willow bark. form of magnesium must also be accessed. In order
The American Pain Foundation has listed the follow- to absorb calcium properly the body required
ing herbs for management of pain: ginseng (for fibro- magnesium. If there is intake of large quantity of
myalgia), kava-kava (for neuropathic pain), St. John’s calcium without magnesium, as an individual may
Wort (for sciatica, arthritis, and neuropathic pain), and develop calcium deficiency. A balanced calcium–
valerian root (for spasms and muscle cramps) (Toy- magnesium supplement may be taken or good
ang et al., 2007; Rigat et al., 2009; Ghosh & Das, 2007; source of magnesium may be accessed through the
Pieroni, 2010; Kumar et al., 2007; Roberts et al., 1998; following foods: spinach, pumpkin seeds, black-eyed
Arun et al., 2013; Biswas & Mukherjee, 2003; Tiwari peas, garbanzos, lentils, and pinto beans, brown rice
et al., 2012; Gantwerker & Hom, 2011; Farnsworth, Ak- and millet, avocados, bananas, and dried figs.
erele, Bingel, Soejarto, & Guo, 1985; Krishnan, 2006; 3. Vitamin C with bioflavonoids:
Dhama et al., 2013a; Stephan & Landis, 2008; Adetutu, Studies currently indicate that individuals or animals
Morgan, & Corcoran, 2011; Hoffman & Pfaller, 2001; with good levels of bioflavonoids in their bodies
Mishra et al., 2007; Abd-Rabou, Zoheir, & Ahmed, 2012; have lower concentration of C-reactive proteins
Hasler, 2005). (the culprit linked with several inflammatory
It is however must be remembered that herbal thera- diseases, cancers, and other illnesses). There are
pies for management of pain is required to be thorough- abundant concentration of vitamin C in citrus fruits,
ly studied, so one needs to be careful while embarking broccoli, Brussels sprouts, tomatoes, green peppers,
on this treatment path. The herbs are not benign which melons, kiwis, strawberries, alfalfa sprouts, and
must be remembered. There are still limitations in re- the skins of potatoes. It is to be importantly noted
search for their safety and efficacy and above all the gov- that bioflavonoids are antioxidants that have got
ernment does not regulate products of herbs for quality. antiallergic, antiinflammatory, antimicrobial, and
So before testing out a herbal remedy the best care is to anticarcinogenic characteristics. They are found
talk to a health care professional for precise use of the in the citrus fruits’ rinds, green peppers, broccoli,
plants (Wanzala et al., 2005; Adetutu et al., 2011; Mishra tomatoes, purple grapes and berries, and certain
et al., 2007; Abd-Rabou et al., 2012). herbal teas.

A. Overview of Pain: Mechanisms of Causation and Treatment by Foods

6 1. Overview of Pain in Livestock: Mechanism to Nutritional Control

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(1995). The welfare of extensively managed dairy cattle—a review. M. Pardo-de-Santayana, A. Pieroni, & R. K. Puri (Eds.), Ethno botany
Applied Animal Behaviour Science, 42(3), 161–182. in the new Europe, people, health and wild plant resources (pp. 16–50).
Hess, J. R., & Greenberg, N. A. (2012). The role of nucleotides in the im- Oxford, UK: Berghahn Books.
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Nutrition in Clinical Practice, 27(2), 281–294. nobotany of food plants in the high river Ter valley (Pyrenees, Cata-
Hesta, M., Ottermans, C., Krammer-Lukas, S., Zentek, J., Hellweg, P., lonia, Iberian Peninsula): non-crop food vascular plants and crop
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26–34. with chronic infectious arthritis of the corpus and osteomyelitis of
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nants: a review. Journal of Dairy Science, 62, 1195–1206. 438–441.
Hoffman, H. L., & Pfaller, M. A. (2001). In vitro antifungal susceptibility Roberts, P. R., Black, K. W., Santamauro, J. T., & Zaloga, G. P. (1998).
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for the Practising of Veterinarian, 18(9), s242–s250. changes in pain sensitivity, prolactin and somatotropin in the pig.
Kent, J. E., Jackson, R. E., Molony, V., & Hosie, B. D. (2000). Effects of Physiological Behaviour, 53(2), 265–270.
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and behaviour of lambs castrated and tail docked with rubber rings infrared thermography to assess inflammation associated with
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alence of leg weakness in broiler chickens and its relationship with Schwartzkopf-Genswein, K. S., Stookey, J. M., dePassille, A. M., &
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8 1. Overview of Pain in Livestock: Mechanism to Nutritional Control

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E., & Hassanali, A. (2005). Ethnoveterinary medicine: a critical re- Yeruham, I., Avidar, Y., Bargai, U., Adin, G., Frank, D., Perl, S., &
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Weary, D. M., Braithwaite, L. A., & Fraser, D. (1998). Vocal responses to opioid receptors in relation to stereotypies, inactivity, and housing
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A. Overview of Pain: Mechanisms of Causation and Treatment by Foods

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 Molded Polystyrene Resins.
Source: Bakelite Corporation, 247 Park Avenue, New York, N. Y.

Small quantities of Resoglas and Trolitul have been imported from

Germany in recent years. Table 9 shows the quantities imported in
recent years.
 Table 9.—Resoglas and Trolitul: United States imports for
consumption, 1933-37

Resoglas (polystyrol) Trolitul

Year
Quantity Value Unit value Quantity Value Unit value
Pounds Pounds
1933 771 (1) 672 (1)
1934 991 (1) 200 (1)
1935 110 $97 $0.88 4,608 $3,782 $0.82
1936 2,220 1,901 .86 4,671 3,641 .78
19372 None None 6,788 4,077 .60

1 Not available.

2 Preliminary.

Source: Analyses of invoices of paragraph 28, act of 1930—U. S. Tariff

Commission.

With the more advanced development of polystyrol resins in

Germany prior to 1938, evidenced by larger commercial production,
by wider application, by the marketing of a water-white product at a
considerably lower price, it might be expected that imports into the
United States would have been in considerably larger amount than
shown in table 9. That they were small was probably due to the high
rate of duty which made them expensive as compared with other
synthetic resins in the United States and thus limited their market to
uses in which the others were less satisfactory. Resoglas was
reported to have been selling for 40 cents per pound in Germany.
The imported resin is assessed for duty under the provisions of
paragraph 28 of the Tariff Act of 1930 at 45 percent ad valorem
based on American selling price (as a competitive product) and 7
cents per pound. The American selling price of the resin made in the
United States until late in 1937, as determined by the Bureau of
Customs, Treasury Department, was $1.85 per pound. The duty was
therefore 90 cents per pound. Imports of Trolitul were valued at 75
cents per pound, giving a cost of $1.75 per pound laid down, duty
paid, in domestic markets. With the present American selling price of
72 cents per pound, the duty would be approximately 36 cents per
pound.
 10. VINYL RESINS
Vinyl acetate, vinyl chloride, and to a lesser extent vinyl
chloroacetate, are the raw materials (monomers) for the several vinyl
resins commercially produced in the United States, Canada, and
Germany. These are all esters of the hypothetical vinyl alcohol and
are made by the action of acetic and hydrochloric acids on
acetylene.
The spontaneous polymerization of vinyl derivatives has been
known for many years, although its significance and industrial
application have been realized only recently. Vinyl acetate, probably
the most important of the vinyl esters, was discovered in 1912 and
first made in Canada in 1917.
Vinyl resins may be classified into (a) polyvinyl acetate, (b)
copolymers of vinyl acetate and vinyl chloride, (c) polyvinyl chloride,
and (d) polyvinyl chloroacetate.

Description and uses.

Polyvinyl acetate resins.—The several commercial types of vinyl
acetate resins are marketed under the trade names Vinyloid A, Alvar,
Gelva, Formvar, and Mowilith. The first of these is a product of
Carbide and Carbon Chemicals Co., New York, the next three are
products of Shawinigan Chemicals Limited, Shawinigan Falls,
Canada, and the last is made by the Interessen Gemeinschaft
Industrie A. G., Germany. Vinyloid A and Gelva represent the
simplest series of vinyl acetate resins and are made by polymerizing
the monomer. The softening point and viscosity of the polyvinyl
acetate resins increase with higher polymerization. Such resins are
colorless, tasteless, odorless, thermoplastic products. They are
soluble in coal-tar solvents and are compatible with certain alkyd
resins, tar-acid resins, and natural resins. Films of polyvinyl acetate
resin are not discolored by exposure, and after irradiation they
become opaque to ultraviolet light, are hard and tough, and have
good adherence and endurance. Their dielectric strength is good
and they do not show a carbon track after the passage of an electric
arc. Various grades having softening points from 80° to 200° C. are
available.
Polyvinyl acetate resins are used in making transparent papers,
paper to metal laminations, glassine papers for food packaging, as a
substitute for chicle in chewing gum, and as a component of paints,
varnishes, and lacquers. They have the desirable properties of
compatibility, durability, resistance to abrasion, and rust inhibition in
the surface-coating use. Having the same refractive index as pyrex
glass, they leave no line of demarcation when used as a cement for
that material. They have been used to stiffen toe-caps in shoes and
articles made from paper pulp suspensions. Gelvas are not molded
as such because of their tendency to cold flow. They are used,
however, as a binder for ground mineral fillers in advertising signs
and for wood flour in molded artificial wood carvings. In nitrocellulose
lacquers they improve the adhesion, luster, and toughness.
Alvars are made by replacing part or all of the acetate groups in
Gelva with acetaldehyde. Their viscosity varies with the degree of
polymerization and their properties vary according to the extent of
replacement of the acetate groups. The Alvar types do not cold flow
when molded, are tougher, harder, and have better adhesion but are
less resistant to weathering than the Gelva types. Other properties
are about the same as those of the Gelvas. Alvars having 70 to 80
percent acetate group replacement are used chiefly in spirit type
varnishes, lacquers, and enamels that must stand exposure to
weather. Another Alvar type is used in injection and press molding.
The high binding power of the resin permits the use of large
percentages of filler without loss of desirable properties. Such
moldings may be machined and polished, and take inserts, such as
the wood core in shoe heels. Flexible phonograph and transcription
records made from the Alvars have gained wide approval. An 85
percent (acetate replacement) type has better impact strength and is
used in toilet articles. Sheets, rods, and tubes of this resin may be
machined in much the same way as nitrocellulose plastic and used
where noninflammability is an asset.
Formvars are made by replacing part or all of the acetate groups
in Gelva with formaldehyde. These resins are colorless, odorless,
tasteless, and thermoplastic. They have higher softening points and
greater tensile and impact strength than the Alvars. They are
resistant to alcohols, coal-tar solvents, fats, oils, or water. Moisture
transmission rate through a film of this resin is about one-tenth that
through regenerated cellulose and one-fourth that through cellulose
acetate.
The grades of the Formvars available are designated by the extent
of replacement of the acetate group. The 75-percent replacement
type has excellent mechanical strength and flexibility and is
unaffected by sunlight. Formvars of 95 percent acetate displacement
have a tensile strength as high as 10,000 pounds per square inch
and offer possibilities in the manufacture of artificial silk and
photographic film.
The vinyl resins have made possible a new type of safety glass
superior to any heretofore marketed. By condensing butylaldehyde
with vinyl acetate, a polymer is obtained which is used as the inner
layer between two sheets of glass. Heat and pressure secure
complete adhesion and yield a sheet with greater resistance to
breakage at low temperatures than the types now in general use.
Although safety glass was invented in 1905, and many substitutes
for the original nitrocellulose inner layer have been proposed, only
two reached commercial importance before the development of the
vinyl resins. These are cellulose acetate and the acrylate resins.
Safety glass used in automobile windshields up to about 1930
discolored after a year or two of service. This discoloration was due
to the action of the actinic rays of the sun on the nitrocellulose layer.
Since 1930 this difficulty has been largely overcome by using an
actinic ray filter glass (a special glass with a high iron content) in
front of the nitrocellulose sheet, or by using cellulose acetate, which
is not discolored to the same extent by light, as a substitute for
nitrocellulose. Both cellulose nitrate and cellulose acetate, however,
have a tendency to lose toughness and strength at low
temperatures, to absorb moisture, and to separate from the glass
around the edge unless sealed, and to lose their plasticizer and
shrink.
Although a vast improvement over ordinary plate glass, laminated
glass made with cellulose nitrate or acetate has the serious defect of
being brittle at low temperatures, such as prevail in the winters of
northern States. It is easily shattered at zero Fahrenheit, while at 60°
F. and above it is quite strong. This shortcoming led to the
development of the vinyl resin sheet for safety glass with a
remarkable degree of toughness. At normal temperatures it has
rubberlike toughness which, although decreased at low
temperatures, is not punctured by the impact of a half-pound steel
ball falling from a 30-foot height at minus 10° F., whereas
nitrocellulose or acetate laminated glass withstands the impact of a
fall from not greater than one-tenth this height. A further advantage
of the vinyl sheet is that it is water resistant, making the sealing of
the edges of the glass unnecessary and thus reducing costs.
Exposure to ultraviolet light in Florida sunlight for more than 2 years
did not discolor it.
The many desirable properties of the vinyl resins, as outlined
above, indicate their widespread use in laminated safety glass when
it is available in sufficient quantities. It is estimated that our annual
output of safety glass interlayer sheets exceeds 17,000,000 pounds,
of which 25 to 30 percent are for windshields, and 70 to 75 percent
for side and back windows of automobiles.
At least one of the series of Mowiliths made in Germany is
polymerized vinyl acetate. It is recommended as an ingredient of
water-white lacquers. It is compatible with nitrocellulose and is
extremely durable and not disintegrated or discolored on exposure to
weather.
Copolymers of vinyl acetate and vinyl chloride.—The simultaneous
polymerization of mixtures of vinyl acetate and vinyl chloride yields
resins with the desirable properties of the two reactants. The extent
of plasticity is largely controlled by varying the ratio of the vinyl
derivatives. Resins high in vinyl chloride content are better suited to
molding, and those high in vinyl acetate are better lacquer
ingredients. These resins are marketed as Vinylites by the Carbide
and Carbon Chemicals Co., New York. They are thermoplastic,
odorless, tasteless, and practically nonflammable. Their outstanding
properties are resistance to water, soap, acids, alkalies, and alcohol,
and their strength and good dielectric properties. Their stability to
light is improved by the addition of ultraviolet absorbing compounds
and their stability to heat by the addition of lead oleate, calcium
stearate, or other bases. Water absorption and compatibility with
other resins is increased as the chloride content increases.
The principal types of copolymers are:
Vinylite VYN, high molecular weight. This resin is used in dentures
where good fatigue resistance, impact strength, and tensile strength
are required. It contains 85 to 88 percent vinyl chloride.
Vinylite VYN, medium molecular weight. This resin is used in
general molding and extending applications including sheets, rods,
and tubes. Its vinyl chloride content averages 85 to 88 percent.
Vinylite VYN, low molecular weight. This resin is used in moldings,
coated paper, lacquers, floor tile, phonograph records, and felt
impregnation. It contains 85 to 88 percent vinyl chloride.
Vinylite VYC. This resin of low molecular weight is compatible with
nitrocellulose and is used in lacquers and finishes for industrial
applications. Lacquers from the Vinylites are called Vinyloids.
The Vinylites for molding are thermoplastic and shrink very little,
making them applicable to large moldings. They may be used in
extension processes such as tooth-brush preforms, pipe lining, and
wall trim. Fillers and pigments may be added, although pigments
containing iron and zinc have harmful effects on the stability of the
resin. The fillers used are wood flour, mica, talc, and alpha cellulose.
Fillers reduce the mechanical strength of the resin and lessen its
resistance to water. Plasticizers, such as dibutyl phthalate or tricresyl
phosphate, give a softer, more flexible resin. Resins from the
copolymers resemble the cellulose derivatives in their molding
characteristics, mechanical strength, and appearance.
In lacquers the Vinylites offer high resistance to water, oils, and
chemicals. The drying of such lacquers is by evaporation rather than
by oxidation. They are suitable for lining food containers, coating
concrete, coating paper for bottle cap liners, and as a stiffener for
box toes of shoes. Their most successful application at present is as
an inside coating for beer cans. Floor tile containing these resins
mixed with slate flour or other filler has good possibilities.
Polyvinyl chloride resins.—Vinyl chloride may be polymerized to
give nonflammable resins of varying solubilities. The completely
polymerized resin is practically insoluble at ordinary temperatures
and is used as a rubber substitute. It is marketed as Koroseal by B.
F. Goodrich Rubber Co., Akron, O. Compared with natural rubber, it
has greater resistance to acids, alkalies, oils, and alcohol, more
flexing life, better resistance to sunlight, water, and oxidation.
Solutions of this resin marketed as Korolac are used in special types
of varnishes.
Polyvinyl chloroacetate resins.—These resins known as Mowiliths
are made in Germany. Application is largely for surface coating.
Practically no information on this type is available.
Divinyl acetylene and synthetic rubber.—Two products closely
related to those described above but probably not synthetic resins as
defined for this discussion are divinyl acetylene, a synthetic drying
oil, and Neoprene, a synthetic rubber.
Acetylene, when passed into a solution of copper chloride and
ammonium chloride, combines with itself. When two molecules of
acetylene react monovinyl acetylene is formed, and when three
molecules of acetylene react divinyl acetylene is formed. Monovinyl
acetylene reacts with hydrochloric acid to give chloroprene, which is
polymerized to synthetic rubber or Neoprene.
Divinyl acetylene is a colorless liquid which darkens on exposure
to light and which has an onionlike odor. When polymerized liquids
are formed, then as the reaction progresses viscous products and
finally insoluble, infusible, inert resins. By arresting the reaction
before the gel point is reached, an amber colored heavy liquid,
soluble in aromatic hydrocarbons, is obtained. Since divinyl
acetylene will continue to polymerize at ordinary temperatures, this
property is taken advantage of in using it as a basis for paints, under
the name “synthetic drying oil.” Clear, amber films are obtained from
solutions of this oil in solvent naphtha. Divinyl acetylene is quick
drying, is many times more impervious to moisture than linseed oil,
and is thermosetting. It is not attacked by solvents but is attacked by
strong oxidizing agents, and the gelled material may ignite
spontaneously.
Although not classified as a resin, synthetic rubber is discussed
here because of its close chemical relationship to the vinyl resins. It
is made commercially by E. I. du Pont de Nemours & Co.,
Wilmington, Del., and is marketed as Neoprene. It is sold as a plastic
polymer which is vulcanized and processed much the same as
natural rubber except that sulphur is not essential to vulcanization.
Synthetic rubber is higher in price than natural rubber, but it has
certain properties which make it suitable for service conditions where
natural rubber is unsatisfactory. Among these properties are its
resistance to gasoline, oils, and greases, and to elevated
temperatures. It does not check or crack on exposure to sunlight, nor
does it oxidize as rapidly as natural rubber. Its principal applications
are in special gaskets, printing rolls, jackets for high tension cable,
linings for gasoline or oil hose lines, balloon fabrics, diaphragms for
regulators, and packing for compressors. Its existence acts as a limit
to the increase in the price of natural rubber and assures a supply in
emergencies.

Production in the United States.

Some of the products described are commercially produced in the
United States; others in Canada or in Germany. Those made in the
United States are usually not made by more than one firm, so that
statistics of production and sales are not publishable. The vinyl
acetate resins have been produced principally in Canada; the
copolymers of vinyl chloride and vinyl acetate are domestic products.
In 1935 the United States output of all vinyl resins exceeded
1,000,000 pounds, a figure that was increased in 1936 and 1937.
The Canadian output of Gelva and Alvar has reached commercial
quantities; that of Formvar is still confined to experimental plant lots.
The acceptance of vinyl resin sheets for safety glass will greatly
increase the output in 1938. The basic patent, known as the
Morrison-Blaike patent, United States No. 2,036,092 issued on
March 31, 1936, is owned by Shawinigan Chemicals, Ltd., Montreal,
Canada, who have licensed several domestic producers. The
monomer (vinyl acetate) is now produced at Niagara Falls, N. Y., by
the Niacet Chemicals Corp., which is jointly owned by this Canadian
firm, Carbide and Carbon Chemicals Corporation, and E. I. du Pont
de Nemours & Co. It is also produced by du Pont at Belle, W. Va. It
is shipped, in tank cars, to polymerization and sheet-forming plants
at Indian Orchard, Mass., Arlington, N. J., and Charleston, W. Va.
The Indian Orchard plant, known as the Shawinigan Resin Products
Co., and jointly owned by the Canadian firm and the Fiberloid
Corporation, is now in operation. The plant of the du Pont Company
at Arlington, N. J., began production in May 1938, and that of
Carbide and Carbon Chemicals Corp, at Charleston, W. Va., is in
production. These plants have a combined annual capacity of about
10 million pounds of vinyl resin sheets. According to present plans
this new safety glass will be available for 1939 model automobiles.
The resin sheet to be used is 0.0015 inch thick as compared with the
0.0025 inch thickness of the present cellulose acetate and
nitrocellulose sheet. Several trade names have been adopted for the
vinyl resin sheets, among which are Vinylite X, and Butvar. The
licenses granted to domestic makers under the Morrison-Blaike
patent also permit them to make vinyl acetate resins for purposes
other than safety-glass sheets. Considerable progress has been
made in adapting these resins to injection molding operations for the
production of tooth-brush handles, combs, closures, and other parts.

Imports into the United States.

 The official statistics of imports of vinyl resins prior to 1936 are not
satisfactory for purposes of comparison. Imports could be entered
under either paragraph 2 or paragraph 11 and could be included
either with the statistics of imports of vinyl acetate (see table 91,
page 141) or be thrown into a general group of non-coal-tar synthetic
gums and resins, n. s. p. f., which in addition to vinyl resins would
include the acrylates and ureas. Table 10 gives imports of synthetic
resins under paragraph 11 of the Tariff Act of 1930.

Table 10.—Synthetic resins classified under paragraph 11:1 United

States imports for consumption 1931-37

Year Quantity Value Unit value

Pounds
1931 453 $173 $0.38
1932 454 29 .06
1933 1,120 496 .44
1934 4,084 1,576 .39
1935 3,105 1,804 .58
1936 146 65 .45
19372 1,963 439 .22

1 Statistical classification 838.914, synthetic gums and resins, n. s. p. f. (not coal

tar) 1931-35; 838.939 same, other than those in chief value of vinyl acetate, 1936
and 1937.
2 Preliminary.

Source: Compiled by the U. S. Tariff Commission from official statistics of the U.

S. Department of Commerce.

A better idea of the imports of vinyl resins prior to 1936 is obtained

by an invoice analysis of imports through the Port of New York under
paragraphs 2 and 11. Table 11 shows imports of vinyl acetate resins
based on such an analysis for 1934 and 1935 and on official
statistics for the years 1936 and 1937.
 Similarly table 12 shows imports of Mowilith resins based upon
import analysis for the period 1932-1935, and upon official statistics
for 1936 and 1937.

Table 11.—Vinyl acetate resins: United States imports for

consumption, 1934-37

Year Quantity Value Unit value

Pounds
19341 42,000
19351 240,000
19362 600,808 $144,782 $0.24
193723 652,730 201,213 .31

1 Invoice analysis of imports entered through the New York customs district.

2 Statistical classification 817.58 (par. 2), vinyl acetate, polymerized, and

synthetic resins made in chief value from vinyl acetate, n. s. p. f. (excluding
imports from Germany) and 838.938 (par. 11), synthetic resins made in chief value
from vinyl acetate, n. e. s.
3 Preliminary.

Source: Compiled by the U. S. Tariff Commission from official statistics of the U.

S. Department of Commerce.

Table 12.—Mowilith resins: United States imports for consumption,

1932-37

Year Quantity Value Unit value

Pounds
19321 555 $229 $0.41
19331 741 247 .33
19341 2,950 1,668 .57
19351 3,372 3,175 .94
19362 7,056 2,410 .34
 193723 220 308 1.40

1 Analysis of invoices of imports entered through the New York customs district.

2 Imports from Germany under statistical classification 817.58 (par. 2), vinyl
acetate, polymerized, and synthetic resins made in chief value of vinyl acetate.
3 Preliminary.

Source: Compiled by the U. S. Tariff Commission from official statistics of the U.

S. Department of Commerce.

Prior to January 1, 1936, the rate of duty on imports of vinyl resins

was 6 cents per pound and 30 percent ad valorem under paragraph
2, and 4 cents per pound and 30 percent ad valorem under
paragraph 11 of the Tariff Act of 1930. Under the terms of the trade
agreement with Canada, the duty under both paragraphs was
reduced to 3 cents per pound and 15 percent ad valorem. This rate
was generalized to the other countries from which we have received
imports, with the exception of Germany.

Exports from the United States.

Exports of vinyl resins are not separately shown in official
statistics.
 11. OTHER SYNTHETIC RESINS
The synthetic resins already discussed are those in substantial
commercial production but, by no means, the only ones known or
produced. Several thousand new ones have been reported and the
search continues in laboratories throughout the world. A successful
new product must be one made from inexpensive raw materials or
must possess some property or advantage that will permit its sale at
a price level above that of other resins.
No attempt is here made to list the host of less important resins.
Certain ones of unusual interest or possessing unique properties are
described below. These include resins obtained from adipic acid,
aniline, citric acid, diphenyl, furfural, lignin, sugar, and sulphonamide.

Adipic acid resins.

The resins from adipic acid are classed as alkyd resins. Those
obtained by the condensation of adipic acid and glycerin are soft and
rubbery and are used to some extent in surface coatings and in
photographic films. In these the resin is formed in three stages as in
other alkyd types: A soluble liquid, a viscous rubbery product, and a
form insoluble in the usual solvents.
Commercial domestic production of these resins was reported for
the first time in 1935 and the output has increased each year since
then.

Aniline resins.
Resins obtained by condensing aniline and formaldehyde have
been developed in recent years. Much of the research on this type of
resin was done in Switzerland by the Ciba Co., which holds a
number of patents on it. The Swiss product, called Cibanite, has
excellent electrical and mechanical properties. At least one domestic
manufacturer is licensed under the Swiss-owned patents.

Citric acid resins.

Considerable interest has recently been manifest in synthetic
resins derived from citric acid. The sharp decline in the price of citric
acid, as a result of large scale synthesis from sugar has placed it
within the realm of possibility as a raw material for synthetic resins.
The citric acid resins, classed as alkyd resins, are obtained by
condensing citric acid and glycerin. Commercial production is said to
have started in Europe, but there is no known domestic production
as yet.

Diphenyl resins.
A series of products known as Aroclors and made by chlorinating
diphenyl are available in commercial quantities.
Diphenyl was commercially produced for the first time by Swann
Research, Inc., at Anniston, Ala., about 1928. The demand for it as a
heat-transfer medium resulted in large scale output. Later it was
found that certain of the chlorinated compounds of diphenyl possess
valuable resin properties.
The Aroclors range from a clear mobile oily liquid to an amber
colored transparent solid. They are thermoplastic, do not polymerize
or oxidize, and are therefore nondrying. They may be dissolved in
varnish oils, such as tung oil and linseed oil, to give varnishes which
are resistant to alkali and water. The diphenyl resins are good
adhesives on metal and glass and give strong joints between such
surfaces. They have a high dielectric constant, resistivity, and a low
power factor. Their chief use is in wire insulation.
The domestic production of chlorinated diphenyls is, at present,
solely by the Monsanto Chemical Company, St. Louis, Mo.
Furfural resins.
Large scale commercial production of furfural, an aldehyde
obtained from oat hulls and other farm waste, has made it available
for synthetic resin manufacture.
Tar-acid furfural resins possess certain outstanding properties,
such as great dimensional accuracy, great reaction speed to the
infusible solid stage, and unusual strength and toughness. They are
available in dark shades only. Printing plates as large as those of
metropolitan daily papers are molded from them as are radio tube
bases, all sorts of electrical parts, and machined parts requiring
great dimensional accuracy. Other uses are in abrasive wheels,
varnishes, and adhesives.
Probably the largest domestic maker of furfural resins is the Durite
Plastics Division of Stokes and Smith Company, Philadelphia, Pa.

Resins from sugar.

Many attempts have been made to utilize sugar as a raw material
for synthetic resins. United States Patent No. 1,949,831, dated
March 6, 1934, claims a process for the manufacture of molding
compounds by condensing saccharide with aldehydes and urea.
Pure sucrose yields a clear, colorless, nonresilient resin, while
molasses and cane sugar give dark-colored resins. The trade name
Sakaloid is used to designate certain of these resins; there is,
however, no known domestic production. Sucrolite is the trade name
of a brand of resins from sugar produced in Europe.

Sulphonamide resins.
The sulphonamide resins were developed from para
toluenesulphonamide, a byproduct obtained in the manufacture of
saccharin (synthetic sweetening agent).
 Para toluenesulphonamide, condensed with formaldehyde or other
aldehyde, forms a viscous mass which, on heating, is converted to a
hard colorless resin. Such resins are compatible with cellulose
acetate or nitrocellulose in lacquers, the combination yielding clear,
colorless lacquers of good gloss and adhesion. Other possible uses
are as an adhesive in safety glass, in certain molding compositions,
in insulating materials, and to deluster artificial silk.
Domestic production of sulphonamide resin is entirely by the
Monsanto Chemical Co., St. Louis, Mo. It is marketed under the
trade name Santolite.
 12. ORGANIZATION OF THE
SYNTHETIC RESIN INDUSTRY
The discussion of the various synthetic resins on pages 11 to 52
carries in each case, under the heading of production, a notation of
the number of companies producing that particular resin; and the
discussion on pages 86 to 141 of important raw materials for these
resins describes briefly the conditions under which these materials
are produced. We shall now consider the interrelationships between
industries producing the several resins, and the relation of the resin
industries to their raw materials and to some of the important resin-
consuming industries.
No description of the organization of a rapidly expanding industry
can be expected to remain accurate for long. But regardless of future
changes that may be expected, the general pattern seems definite
enough to make possible a few broad generalizations. At present the
producers of synthetic resins may be classified in two groups: those
making alkyd and tar-acid resins, and those making all other
synthetic resins.
The alkyd resins and the tar-acid resins are produced in large
volume, and for these resins the patent situation is such that there is
nothing to exclude new producers. The result has been that new
firms have entered the field and there has been a marked tendency
for concerns using these resins on a large scale to produce them.
This general situation may be expected to continue as long as the
volume of consumption of these resins is rising. But when
consumption levels off, it would not be surprising if increased
competition for new business resulted in consolidations of some of
the producing units.
Each of the other synthetic resins is produced by a small number
of firms and this may be expected to continue as long as the
production of a particular resin is small, or basic patents dominate
the situation. When and if the situation in these respects changes for
some of the other resins, they will probably develop the same
tendencies as now exist in the production of the tar-acid and alkyd
resins.

Horizontal relationships between resin

producers.
Horizontal relationships between companies are those between
different units in the same industry (say two tar-acid resin
producers), or in different industries each operating at the same
stage of industrial production (say a tar-acid resin producer and a
producer of urea resin). As a rule, extensive horizontal relationships
are not common in relatively young industries, and this is true of the
production of synthetic resins. In general, it has not been necessary
to absorb competitors to achieve a greater volume of sales, and
efforts have been directed to exploiting the possibilities of expansion
in a growing market. This necessitated solving technical problems
concerning improvement of the product and its production on an ever
larger scale; legal problems regarding patents (protection of those
owned, and the policy to be adopted toward unadjudicated patents
owned by others); and the marketing problem of convincing
prospective customers of the worth of a new product. These and
other problems incidental to successful competitive production and
sale of a given type of synthetic resin have been sufficient to restrain
the desire to produce more than one type.
The patent situation of most synthetic resins is extremely
complicated. In the case of tar-acid molding resins the basic
Baekeland patents have expired, but for other synthetic resins either
the basic patent is still in force, or it is difficult to say which is the
basic patent, because of lack of adjudication by the courts. In all
cases dozens of supplementary patents are in force and sometimes
hundreds. As a result the patent situation, though one of the bars
against entering into a new field, frequently forces some relationship
between producing units in the same synthetic resin field. Cast