ChapterPDF Available

Water as a photoacceptor, energy transducer and rechargeable electrolytic biobattery in photobiomodulation.



Objective: In this personal view, we propose that the modulation of the structure and function of water by light may come to embody a new mechanistic approach for the treatment of complex diseases. Background data: Long considered an innocuous medium, water has increasingly been found to be a key player in numerous mechanisms, including first-contact events in which cells decide between survival and apoptosis. Consequently, externally applied electromagnetic energy (light) may selectively target the organization of water to steer biological function. Methods: We survey light-water research with particular emphasis on the quasi-crystalline exclusion zone (EZ), part of the cell's aqueous interface that is just now beginning to be decoded. The current state of research, the technical challenges involved in obtaining evidence in biological systems, and some potential uses and implications of EZ water in medicine are presented. Results: Though existing data have not yet proven the role of EZ water in photobiomodulation, research shows that EZ water can store charge and can later return it in the form of current flow, with as much as 70% of the input charge being readily obtainable. Macroscopic separation of charges can be stable for days to weeks and has unusual electric potential. Water is, thus, an unexpectedly effective charge separation and storage medium. Conclusions: We propose that the EZ may be selectively targeted in photobiomodulation as an efficient energy reservoir, which cells can use expeditiously to fuel cellular work, triggering signaling pathways and gene expression in the presence of injury-induced redox potentials.
This timely book nicely summarizes the few, currently known, mechanisms underlying
photobiomodulation (PBM) in the context of their most promising applications within a wide
variety of halth care disciplines. Its perspectives range from enthusiastic acceptance and
promotion of PBM applications to the more healthy encouragement of still much needed clinical
Dr. Donald Pathoff
Foundation for Photobiomodulation Research, USA
Laser therapy is today a reality for professionals in health care. At the same time, it is still a hot
topic for research with many challenges to be overcome. This book puts together fundamental
concepts and applications in a single resource, creates opportunities to multiply the potential
users, and provides a summary of the state of the art in the field. The authors are prominent in
their fields, for which the book will certainly prove to be an important reference.
Prof. Vanderlei S. Bagnato
University of São Paulo, Brazil
Low-level laser (light) therapy (LLLT) and photobiomodulation (PBM) are almost 50 years
old and recently have been getting increasing acceptance from the scientific, medical, and
veterinary communities. Discoveries are constantly being made about the cellular and
molecular mechanisms of action, the range of diseases that can be treated is rising, and
home-use LED devices are becoming common.
This book compiles cutting-edge contributions from the world’s leading experts in
LLLT and PBM. The chapters cover general concepts, mechanisms of action, in vitro studies,
pre-clinical animal studies, veterinary applications, and a wide range of clinical topics. The
book appeals to anyone involved in the basic science, translational aspects, and clinical
applications of LLLT and PBM.
Michael R. Hamblin is a principal investigator at the Wellman Center for
Photomedicine at Massachusetts General Hospital, Boston, USA, and an
associate professor of dermatology at Harvard Medical School and the
Harvard-MIT Division of Health Science and Technology, Massachusetts, USA.
His research interests lie in the areas of photodynamic therapy and LLLT.
Marcelo Victor Pires de Sousa is founder and chief scientist at Bright
Photomedicine, São Paulo, Brazil. He received his PhD on the topic “Physics
Applied to Neuroscience” from the Institute of Physics, University of São Paulo,
Brazil, and is involved in the development of new products and dissemination
of photomedicine.
Tanupriya Agrawal obtained her MD from Netaji Subhash Chandra Bose
Government Medical College, Jabalpur, India, and a PhD in biomedical sciences
from Creighton University, Omaha, Nebraska. She is a visiting postdoctoral
fellow at Dr. Hamblin’s lab at the Wellman Center for Photomedicine. She is also
a trainee pathology resident at Tufts Medical Center, Boston, USA.
de Sousa
Michael R. Hamblin
Marcelo Victor Pires de Sousa
Tanupriya Agrawal
edited by
Handbook of Low-Level Laser Therapy
Handbook of Low-Level
Laser Therapy
ISBN 978-981-4669-60-3
Handbook of Low-Level
Laser Therapy
Michael R. Hamblin
Marcelo Victor Pires de Sousa
Tanupriya Agrawal
edited by
Handbook of Low-Level
Laser Therapy
July 16, 2016 11:1 PSP Book - 9in x 6in 00-Hamblin-prelims
Published by
Pan Stanford Publishing Pte. Ltd.
Penthouse Level, Suntec Tower 3
8 Temasek Boulevard
Singapore 038988
British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library.
Handbook of Low-Level Laser Therapy
Copyright c
2017 Pan Stanford Publishing Pte. Ltd.
All rights reserved. This book, or parts thereof, may not be reproduced in any
form or by any means, electronic or mechanical, including photocopying,
recording or any information storage and retrieval system now known or to
be invented, without written permission from the publisher.
For photocopying of material in this volume, please pay a copying
fee through the Copyright Clearance Center, Inc., 222 Rosewood Drive,
Danvers, MA 01923, USA. In this case permission to photocopy is not
required from the publisher.
ISBN 978-981-4669-60-3 (Hardcover)
ISBN 978-981-4669-61-0 (eBook)
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To my beautiful wife Angela to whom I have been devoted
for thirty-six years
—Michael R. Hamblin
To my beloved wife Vivianne with whom I celebrate this
book and all other achievements
—Marcelo Victor Pires de Sousa
Dedicated to my parents, my beloved husband, and my
daughter, Aashi
—Tanupriya Agrawal
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July 16, 2016 11:1 PSP Book - 9in x 6in 00-Hamblin-prelims
Preface xxxiii
1 What is Low-Level Laser (Light) Therapy? 1
Marcelo Victor Pires de Sousa
1.1 Introduction 1
1.2 Fundamental Science: Optics, Photochemistry, and
Photobiology 5
1.2.1 Tissue Optics 6
1.2.2 Photochemistry of Chromophores 7
1.2.3 Photobiology: Mechanisms of LLLT Effects 8
1.3 Research in LLLT 9
1.4 Clinical and Biomedical Applications of LLLT 11
2 History of Low-Level Laser (Light) Therapy 17
Michael R. Hamblin
3 Lasers, LEDs, and Other Light Sources 35
James Carroll
3.1 Introduction 35
3.2 State of the Art 37
3.3 History of Devices 38
3.4 Nomenclature 38
3.5 Laser Classification 39
3.6 Light Sources and Properties 40
3.6.1 Different Properties of Laser and LED Light
Sources 40 Wavelength 40 Coherence 42 Power 42
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viii Contents Irradiance 42 Penetration 43 Pulses 44 Collimation 46 Spectral Width (Monochromaticity) 47 Stability 47 Polarization 47 Beam Area 48 Scanning vs. Contact Method 48
3.7 Summary on Light Sources and Properties 49
4 Is Coherence Important in Photobiomodulation? 51
Toma s H o d e
4.1 Introduction 51
4.2 Is Coherence Lost Upon Entering Tissue? 53
4.2.1 How Fast is Too Fast? 55
4.3 What Biological Significance Could Speckles Have? 56
4.3.1 Intensity Thresholds 56
4.3.2 Polarization 58
4.3.3 Dynamic Environment 60
4.4 Summary 61
5 Tissue Optics 67
Bryan James Stephens and Linda Ramball Jones
5.1 Optical Properties of Tissues 67
5.1.1 Tissue with Weak Scattering 68
5.1.2 Tissue with Strong (Multiple) Scattering 68
5.1.3 Full Picture of Penetration 70
5.1.4 Optical Properties of Water 70
5.1.5 Optical Properties of Blood 73
5.1.6 Spectral Variation of Optical Properties 74
5.2 Methods and Algorithms for the Measurement of
Optical Parameters of Tissues 77
5.2.1 Integrating Sphere Technique 78
5.2.2 Kubelka–Munk Model 78
5.2.3 Inverse Methods 79
5.3 Methods and Algorithms for the Simulation of the
Light Interactions within Tissues 79
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Contents ix
5.3.1 Monte Carlo Simulation 80
5.3.2 Optical Tissue Phantoms 81
5.4 Practical Implementation 83
6 Light–Tissue Interaction and Light Dosimetry 87
Ana Carolina de Magalh˜
aes and Elisabeth Mateus Yoshimura
6.1 Light–Tissue Interactions 87
6.2 Light Dosimetry 96
7 Mitochondrial Light Absorption and Its Effect on ATP
Production 101
Nicolette Houreld
7.1 Mitochondria 102
7.1.1 Adenosine Triphosphate (ATP) Synthesis 102
7.2 Phototherapy 104
7.2.1 Effect of Phototherapy on Mitochondria and
ATP Synthesis 105
7.3 Conclusion 113
8 Water as a Photoacceptor, Energy Transducer, and
Rechargeable Electrolytic Bio-battery in
Photobiomodulation 119
Luis Santana-Blank, Elizabeth Rodr´
us A. Santana-Rodr´
ıguez, Karin E. Santana-Rodr´
and Heberto Reyes-Barrios
8.1 Introduction 120
8.2 Absorption and Transport of Light Energy by Water 122
8.3 Photo-Infrared Pulsed Biomodulation 125
8.4 Water Oscillator Paradox 126
8.4.1 Bulk Water 127 Application I: Light energy absorption
and enhanced ATP 127 Application II: Light-modulated
biomolecular motors and pumps in
aqueous media 128
8.4.2 Confined-Space Water 129
8.4.3 Interfacial Water: What is EZ? 130
8.5 Metabolism and Scaling Laws 134
8.6 Conclusion 134
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9 Role of Reactive Oxygen Species in Low-Level Laser
Therapy 141
Vikrant Rai
9.1 Mitochondrial Response to LLLT 142
9.2 LLLT-Induced Production of ROS 143
9.2.1 Cytochrome 143
9.2.2 Flavins 144
9.2.3 Porphyrins 145
9.3 Role of Reactive Oxygen Species 148
9.3.1 Oxidative Stress at Cellular Level Due to ROS 148
9.3.2 Antioxidant Effect of LLLT 149
9.3.3 Cellular Response to Increased ROS (Oxidative
Stress) 149
9.3.4 Response of Various Transcription Factors to
Oxidative Stress 151
9.3.5 ROS-Mediated Effect of LLLT on Nervous
System 153
9.3.6 ROS-Mediated Apoptosis 155
9.3.7 ROS Effect on Thrombosis and Hemostasis 156
9.3.8 ROS-Mediated Effect of LLLT on
Musculoskeletal System 157
9.3.9 ROS-Mediated Effect of LLLT on Oral Cavity 158
9.3.10 ROS-Mediated Effect of LLLT on Lungs 158
10 Molecular Basis for Photobiomodulation: Light-Induced
Nitric Oxide Synthesis by Cytochrome c Oxidase in
Low-Level Laser Therapy 165
Robert Oliver Poyton and Marina Hendrickson
10.1 Introduction 165
10.2 Cytochrome c Oxidase: A Photoreceptor for LLLT 166
10.3 Structure/Function of Mitochondrial Cytochrome c
Oxidase 167
10.4 Enzymatic Activities of Cytochrome c Oxidase 169
10.4.1 Regulation of Cox/H2O Activity 170
10.4.2 Regulation of Cox/NO Activity 171
10.5 Low-Intensity Light Stimulates Cox/NO but Not
Cox/H2O Activity 173
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Contents xi
10.5.1 Possible Mechanism for Light Stimulation
of Cox/NO 173
10.6 Cox/NO, NO, and LLLT 174
10.7 Summary 177
11 Cytoprotective Effect of Low-Level Light Therapy using LEDs
on Neurons 185
Margaret Wong-Riley and Huan Ling Liang
11.1 Introduction 186
11.2 Role of Cytochrome c Oxidase in
Photobiomodulation of Cultured Visual Cortical
Neurons 186
11.3 Neuroprotective Effect of 670 nm LED on Primary
Neurons Inactivated by Cyanide 190
11.4 Neuroprotective Effect of 670 nm LED on Primary
Neurons Poisoned by MPP+and Rotenone:
Implications for Parkinson’s Disease 193
11.5 Neuroprotective Effect of Pretreatment with
670 nm LED on Primary Neurons Exposed to KCN,
Rotenone, or MPP+196
11.6 Neuroprotective Effect of 670 nm LED on
Cytochrome c Oxidase Activity of Deprived Visual
Cortex of Monocularly Enucleated Rats 199
11.7 cDNA Microarray Analysis of Genes Up- and
Down-Regulated by 670 nm LED in Deprived Visual
Cortex of Monocularly Enucleated Rats 201
11.8 Conclusion 203
12 Low-Level Laser and Cultured Neural Tissue 207
Patricia J. Armati and Roberta T. Chow
12.1 Why Use Cell or Tissue Culture Models? 207
12.2 Cell Lines 208
12.3 Specific Characteristics of Nervous System Cells 209
12.4 LLL, Cell Culture, and Peripheral Nervous
System 211
12.5 Delivery of LLL to Neural Tissue in Culture 215
12.6 LLL Irradiation of Cultured Sensory Neurons in
Pain-Related Studies 215
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xii Contents
12.7 Low-Level Laser: Excitatory or Inhibitory 216
12.8 Dorsal Root Ganglion Cultures of Nociceptor
Neurons 218
12.9 LLL Effects on Sympathetic Nervous System
Neurons 224
12.10 Central Nervous System in Culture 225
13 Shining a Light on Parkinson’s Disease 237
Daniel McKenzie Johnstone, C´
ecile Moro, Jonathan Stone,
Alim-Louis Benabid, and John Mitrofanis
13.1 Introduction 238
13.2 Overview of Parkinson’s Disease 238
13.3 Evidence for Neuroprotection by NIR Treatment in
Parkinson’s Disease 239
13.4 How Does NIR Work to Neuroprotect: Two
Mechanisms of Action? 244
13.5 NIR Treatment in Parkinson’s Disease Patients: Can
It Work? 245
13.6 Developing Methods for Intracranial NIR Delivery 247
13.7 Conclusion 247
14 Low-Level Laser Therapy and Stem Cells 253
Qi Zhang, Chang Zhou, and Tingting Dong
14.1 Mechanisms of LLLT Action in Stem Cells 254
14.1.1 Low-Level Laser Irradiation 254
14.1.2 Mechanisms of LLLT 254
14.1.3 Effects of LLLT 256
14.2 Effects of LLLT on Stem Cells 258
14.2.1 Hematopoietic Stem Cells 258
14.2.2 Mesenchymal Stem Cells 259
14.2.3 Adipose-Derived Stem Cells 261
14.3 Clinical Applications of LLLT on Stem Cells 261
14.3.1 LLLT for Stem Cell Transplantation 261
14.3.2 LLLT for Wound Healing and Skin
Restoring 262
14.3.3 LLLT for Neural Regeneration 263
14.3.4 LLLT for Treatment of Hair Loss 264
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Contents xiii
15 Antimicrobial Photodynamic Therapy 273
Vanderlei Salvador Bagnato, Cristina Kurachi,
Kate Cristina Blanco, and Natalia Mayumi Inada
16 Low-Level Laser (Light) Therapy for Wound Healing in
Animal Models 285
e Luiz Oliveira Ramos, Felipe Scholz Ramos, and
Marcelo Victor Pires de Sousa
16.1 Physiology of Wound Healing 286
16.1.1 Mechanisms of Wound Healing with LLLT 286
16.1.2 Types of Wound Healed by LIB 293
16.2 Thrombosis 295
16.3 LLLT Influence on Infected Wounds 296
17 Low-Level Laser Therapy for Arthritis in Animal Models:
Beneficial Effect and Action Mechanism 303
Flavio Aimbire and Paulo de Tarso Camilo de Carvalho
18 Low-Level Laser Therapy for Lung Diseases: From the Bench
to the Bed 317
Flavio Aimbire
18.1 Introduction 317
18.2 Asthma 319
18.2.1 Clinical Studies 319
18.2.2 Experimental Studies 323
18.3 Acute Respiratory Distress Syndrome 327
18.3.1 Clinical Studies 327
18.3.2 Experimental Studies 328
18.4 Chronic Obstructive Pulmonary Disease 331
18.4.1 Clinical Studies 331
18.4.2 Experimental Studies 332
18.5 Pneumonia 332
18.5.1 Clinical Studies 332
18.6 Tuberculosis 333
18.6.1 Clinical Studies 333
19 Low-Level Laser (Light) Therapy in Tendon Healing in
in Vitro and in Vivo Models 339
Lucas F. de Freitas and Michael R. Hamblin
19.1 Introduction 340
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xiv Contents
19.2 Low-Level Light Therapy and Inflammation 344
19.3 Applications of Low-Level Light in Tendon Healing 346
19.3.1 In Vitro Studies 346
19.3.2 In Vivo Studies 347
19.3.3 LEDs Used in Tendon Healing 351
19.4 Conclusion 352
20 Bone Repair in Animal Models 357
Antonio Luiz B. Pinheiro, Luiz G. Pinheiro Soares,
and Aparecida Maria C. Marques
20.1 Introduction 357
20.1.1 Bone Tissue 357
20.1.2 Autologous Bone Grafting and Biomaterials 359
20.1.3 Guided Bone Regeneration 360
20.1.4 Phototherapy 361
20.2 Light Therapies in the Bone Repair of Animal
Models 361
20.3 Closing Remarks 364
21 Transcranial Low-Level Laser (Light) Therapy for Stroke and
Traumatic Brain Injury in Animal Models 371
Michael R. Hamblin, Luis De Taboada,
and Ying-Ying Huang
21.1 Introduction 372
21.2 Photobiology of Low-Level Laser Therapy 373
21.3 LLLT on Neuronal Cells 375
21.4 Human Skull Transmission Measurements 376
21.5 Epidemiology of Stroke 378
21.6 Mechanisms of Brain Injury after Stroke 379
21.7 Thrombolytic Therapy of Stroke 381
21.8 Investigational Neuroprotectants and
Pharmacological Intervention 382
21.9 Transcranial LLLT for Stroke 382
21.9.1 Transcranial LLLT in Animal Models for
Stroke 382
21.10 Traumatic Brain Injury 385
21.10.1 Transcranial LLLT Studies for TBI in
Animal Models 386
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Contents xv
21.10.2 Effect of Different Laser Wavelengths in
tLLLT in Closed-Head TBI Model in Mice 388
21.10.3 Effect of Pulsing in LLLT for CCI-TBI in Mice 389
21.10.4 Effects of tLLLT-Repetition Regimen in
CCI-TBIinMice 391
21.10.5 Transcranial tLLLT in Mice with TBI
Stimulates the Brain to Repair Itself 393
21.11 Conclusion 395
22 Phototherapy in Peripheral Nerve Repair and Muscle
Preservation 403
Shimon Rochkind
22.1 Incomplete Peripheral Nerve Injury 405
22.2 Complete Peripheral Nerve Injury 407
22.3 Nerve Cells 409
22.4 Clinical Trial 410
22.5 Denervated Muscle 410
22.6 Conclusion 412
23 Low-Level Laser Therapy for Spinal Cord Repair 415
Takahiro Ando and Michael R. Hamblin
23.1 Introduction 415
23.2 Therapeutic Strategies for Spinal Injury 416
23.3 LLLT for Spinal Cord Repair 418
23.3.1 Laser Irradiation in Spinal Cord for
Therapy of Injured Peripheral Nerves 418 Animal studies 418 Clinical studies 420
23.3.2 LLLT for Nerve Transplantation of Spinal
Injured Animals 421
23.3.3 Effects of NIR Laser Irradiation Alone for
SCI Model 423 Experimental SCI model 423 Transmittance of transcutaneous
NIR laser to spinal cord 423 LLLT for injured spinal cord in
rats 425
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xvi Contents
23.3.4 Clinical Study: Intravascular LLLT for
Chronic SCI Patients 427
23.4 Mechanism Studies of LLLT for SCI 428
23.5 LLLT for Other Spinal Cord Diseases 429
23.6 Conclusion 429
24 Low-Level Laser (Light) Therapy for the Treatment of Visual
System Injury and Disease 435
Janis T. Eells, Sandeep Gopalakrishnan, Michele M. Salzman,
Krisztina Valter, Jan Provis, Ricardo Natoli, John Mitrofanis,
Jonathan Stone, and Melinda Fitzgerald
24.1 Introduction 435
24.2 LLLT in Animal Models of Retinal and Optic Nerve
Injury 437
24.2.1 Methanol Intoxication 437
24.2.2 Light-Induced Retinal Damage 438
24.2.3 Optic Nerve Injury 440
24.3 LLLT in Animal Models of Retinal and Optic Nerve
Disease 441
24.3.1 Retinopathy of Prematurity 441
24.3.2 Diabetic Retinopathy 442
24.3.3 Retinitis Pigmentosa 443
24.3.4 Aging and Age-Related Macular
Degeneration 444
24.3.5 Parkinson’s Disease 444
24.4 LLLT in Clinical Investigations of Retinal Disease 445
24.4.1 Age-Related Macular Degeneration 445
24.4.2 Diabetic Retinopathy 446
24.5 Conclusion 447
25 Protection from Cardiac Ischemia and Reperfusion Injury 453
Agnes Keszler, Svjetlana Dosenovic, and
Martin Bienengraeber
25.1 Introduction 453
25.2 Repair of the Infarcted Heart 454
25.2.1 Underlying Mechanisms of Light-Induced
Repair after Myocardial Infarction 455
25.2.2 Induction of Stem Cells by Phototherapy 457
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Contents xvii
25.3 Protection Against Acute Ischemia and Reperfusion
Injury 457
25.3.1 Alternative Sources of Nitric Oxide in
Light-Induced Cardioprotection 458
25.3.2 Cytochrome c Oxidase and NO 460
25.4 Discussion of Potential Clinical Applications 462
25.5 Conclusion 464
26 Low-Level Laser and Experimental Aortic Aneurysm:
Mechanisms and Therapeutic Implications 471
Lilach Gavish and S. David Gertz
26.1 Introduction 471
26.1.1 Aortic Elasticity and Resilience 472
26.1.2 Smooth Muscle Cells 473
26.1.3 Activated Monocytes/Macrophages 473
26.2 Effect of LLL on Experimental AAA 474
26.2.1 LLL Promotes SMC Proliferation and
Augments Collagen Synthesis in Vitro 474 Proliferation 474 Collagens I and III trihelix
formation 475 Collagen secretion 476 MMP activity 476
26.2.2 LLL Attenuates LPS-Induced Secretion of
Inflammatory Factors 476 Chemokine/cytokine expression 477
26.2.3 LLLI Prevents de Novo Formation and Halts
Further Progression of Pre-Induced AAA
in Vivo 477 De novo aneurysm formation 478 Progression of pre-existing
aneurysm 479
26.2.4 LLL Increases SMC Size and Collagen
Deposition 479 Medial SMC size 479 Collagen reinforcement 479
26.2.5 LLL Attenuates the Number of
Macrophages in Transmedial Aortic
Defects 481
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xviii Contents Macrophages in area of
transmedial defect 481
26.3 Therapeutic Approaches 483
26.3.1 Current Treatments and Early Detection 483
26.3.2 How Can LLL be used for Treatment of
AAA? 483 Noninvasive LLL 484 Minimally invasive intravascular
LLL 484 Minimally invasive laparoscopic
LLL 484
26.4 Conclusion 484
27 Low-Level Laser Therapy: A Treatment Modality for
Multiple Sclerosis Targeting Autoimmunity and Oxidative
Stress 491
Zenas George, Miguel A. Tolentino, and Jeri-Anne Lyons
27.1 Introduction 492
27.1.1 Multiple Sclerosis 492
27.1.2 Pathogenesis of Multiple Sclerosis 493
27.1.3 Animal model for Multiple Sclerosis 494
27.2 LLLT as an Emerging Treatment Modality for
Multiple Sclerosis 494
27.2.1 Efficacy of Phototherapy in Animal Model
for Multiple Sclerosis 494
27.2.2 LLLT for Treatment of MS 496
27.3 Future Directions 497
27.4 Conclusion 498
28 Low-Level Laser Therapy as an Alternative Treatment for
Snake Envenomation 503
Camila Squarzoni Dale and Stella Regina Zamuner
28.1 Introduction 503
28.2 Snake Envenomation of the Brothrops Genus 504
28.2.1 Local Manifestations 506
28.2.2 Systemic Manifestations 506
28.2.3 Anti-Venom Treatment 507
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Contents xix
28.3 Low-Level Laser Therapy for Treatment of Local
Manifestations of Bothrops Envenomation 508
28.3.1 Myonecrosis and LLLT 508
28.3.2 Local Inflammation and LLLT 511
28.3.3 Hyperalgesia and LLLT 512
28.4 Conclusion 513
29 Veterinary Low-Level Laser (Light) Therapy Applications for
Companion Animals 519
Richard L. Godine
29.1 Introduction: Finding Common Ground 519
29.2 Treatment Parameters 521
29.3 Musculoskeletal Conditions 522
29.3.1 Degenerative Joint Disease and
Osteoarthritis 522 DJD of the hip 522 DJD of stifle 526 DJD of elbow 526
29.3.2 Acute Musculoskeletal Injuries 527 Iliopsoas strain 527 Biceps and supraspinatus tendon
strain of the shoulder 529 Fractures 529
29.4 Dermatological Conditions 530
29.4.1 Surgical Wounds and Lacerations 530
29.4.2 Infected Wounds 530
29.4.3 Hot Spots and Otitis Externa 531
29.4.4 Snake and Insect Bites 531
29.5 Neurological Conditions 533
29.5.1 Intervertebral Disk Disease 533
29.5.2 Dementia 534
29.6 Renal Conditions 536
29.6.1 Feline Lower Urinary Tract Disease 536
29.6.2 Chronic Renal Failure 537
29.7 Other Internal Organs 537
29.8 Other Miscellaneous Applications for Light Therapy 538
29.8.1 Dental Applications 538
29.8.2 Ophthalmic Disorders 538
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xx Contents
29.8.3 Neoplasia 538
29.9 Conclusion 539
30 Emergence of Low-Level Laser (Light) Therapy in Clinical
Veterinary Practice 543
Ronald E. Hirschberg
30.1 Introduction: Factors Influencing Adaptation of
LLLT to Clinical Practice 544
30.1.1 Clinical Applications 545 Soft tissue, wound healing, and
ophthalmological applications 545 Spinal cord disease 546 Orthopedic conditions 548 Dermatology and light therapy 549 LLLT and metabolic disease 550
30.1.2 Treatment Parameters 551
30.1.3 Therapeutic Outline 553
30.1.4 Safety and Contraindications 554
30.1.5 Clinical and Practical Benefits of LLLT 555
30.1.6 Future of Photobiomodulation in
Veterinary Practice 557
31 Photomedicine for Exotic Animals: A Case-Based Discussion 559
Narda G. Robinson
31.1 Introduction 559
31.2 Hurdles 559
31.3 Clinical Applications 560
31.3.1 Traumatic Brain Injury 560
31.3.2 Spinal Cord Injury 562
31.3.3 Neuropathic and Orthopedic Pain 564
31.3.4 Wound Healing and Infection 565
31.3.5 Laser Acupuncture 569
31.4 Conclusion 574
32 Recalcitrant Wound: Using Low-Level Laser (Light) Therapy
to Manage Non-Healing Wounds and Ulcers 581
Raymond J. Lanzafame and Istvan Stadler
32.1 Introduction: An Overview of Normal Wound
Healing 582
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Contents xxi
32.2 Photobiomodulation and Wound Healing 583
32.2.1 Photobiomodulation and Its Mechanisms 583
32.2.2 Applying Phototherapy to Wounds:
Wavelengths and Energy Density 584
32.2.3 Applying Phototherapy to Wounds:
Irradiance, Exposure Time, and Dose and
Treatment Frequency 585
32.2.4 Applying Phototherapy to Wounds: Skin
Pigmentation and Other Considerations 586
32.3 Bacterial Contamination and Wound Infection:
Antimicrobial Effects of LLLT 586
32.4 General Considerations for Wound Management 587
32.4.1 Initial Evaluation and Management 587
32.4.2 Evaluation of the Wound or Wounds 588
32.4.3 Wound Evaluation: Initial Documentation
and Management 588
32.4.4 Wound Evaluation: Photodocumentation 589
32.5 Clinical Applications and Considerations 591
32.5.1 Patient Selection 592
32.5.2 Device Selection and Use 592
32.6 Summary 593
33 Clinical Applications with Low-Level Laser Therapy in
Arthritis 597
Jan M. Bjordal
33.1 Introduction 597
33.2 Pathoanatomy and Inflammation in Early-Stage OA
and Avenues for LLLT Irradiation 600
33.2.1 Synovia 600
33.2.2 Bone 601
33.2.3 Cartilage and Meniscii 601
33.2.4 Peripheral Nerves and Pain Receptors 601
33.3 Complex Relationship between Inflammation,
Tissue Interaction, and Structural Chondral Matrix
Degeneration in OA 602
33.4 Why LLLT Works in OA? 602
33.5 Recommended Doses of LLLT in Arthritis 603
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xxii Contents
34 Use of Low-Level Laser Therapy and Light-Emitting Diode
Therapy to Improve Muscle Performance and Prevent
Damage: From Animal Models to Clinical Trials 609
Cleber Ferraresi, Nivaldo Parizotto, Vanderlei Bagnato, and
Michael R. Hamblin
34.1 Introduction 609
34.2 Experimental Models Using LLLT to Enhance
Muscle Performance and Prevent Damage 610
34.3 Experimental Models Using LEDT to Enhance
Muscle Performance and Damage Prevention 613
34.4 Clinical Trials Using LLLT to Increase Muscle
Performance and Prevent Damage: Acute
Responses 619
34.5 Clinical Trials Using LLLT to Enhance Muscle
Performance and Damage Prevention: Chronic
Responses 623
34.6 Clinical Trials Using LEDT to Improve Muscle
Performance and Prevent Damage: Acute
Responses 623
34.7 Clinical Trials Using LEDT to Improve Muscle
Performance and Prevent Damage: Chronic
Responses 634
34.8 Conclusion 634
35 Low-Level Laser Therapy of Pain: Clinical Applications 641
Roberta T. Chow
35.1 Background 641
35.2 What is Pain? 642
35.3 Types of Pain and Mechanisms 642
35.4 Mechanisms Underlying Pain Relief 644
35.4.1 Neural Blockade 644
35.4.2 Reduce Inflammation 645
35.4.3 Reduce Edema 646
35.4.4 Reduce Muscle Spasm 647
35.4.5 Tissue Repair 647
35.4.6 Release of Neurotransmitters 648
35.5 Conditions in Which LLLT is Used and Evidence 648
35.5.1 Reviews of LLLT and Pain 648
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Contents xxiii
35.5.2 Evidence for Specific Conditions 649 Arthridities 649 Neck pain 651 Back pain 651 Shoulder pain 653 Tendinopathy and enthesitis 653 Lateral epicondylitis 653 Trigger point and myofascial
pain 654 Neuropathic pain 655 Lymphedema 656 Post-operative pain 657
35.6 Pretreatment Pain Relief 657
35.6.1 Unique Effects of LLLT in Pain 658
35.7 Practical Considerations 658
35.7.1 Treating Knee Osteoarthritis as an
Example 659
35.8 Factors Influencing Outcomes 660
35.8.1 Laser Factors 660 Wavelength 660 What is the correct dose? 663 Application technique 663
35.8.2 Treatment Protocol 664 How long should a course of
treatment be? 664
35.8.3 Patient Factors 665
35.8.4 Disease Factors 665
35.9 What Are the Goals of Treatment with LLLT? 666
35.9.1 Monotherapy versus Adjunctive
Treatment 666
35.9.2 Why Some Patients Do Not Respond to
LLLT? 666
35.10 Practice Points 667
35.11 “Tip of the Iceberg” Principle 668
35.12 Prognostic Factors 669
35.13 Side Effects of Treatment 669
35.14 Conclusion 669
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36 Low-Level Laser Therapy and Its Application in Tinnitus 685
Alessandra Nara de Souza Rastelli,
Emanuelle Teixeira Carrera, Gustavo Nicolodelli,
and Michael R. Hamblin
36.1 Introduction 686
36.2 Symptoms of Tinnitus Ringing in Ears 688
36.3 Types of Tinnitus 688
36.3.1 Subjective Tinnitus 688
36.3.2 Objective Tinnitus 689
36.3.3 Function and Dysfunction of Inner Ear 690
36.4 Causes of Tinnitus 691
36.5 Diagnosis of Tinnitus 692
36.6 Mechanisms of LLLT on Tinnitus 693
36.7 LLLT for Tinnitus 695
36.8 Conclusion 703
37 Laser Therapy for the Treatment of Radiculopathy 711
Jerome M. True and Luis C. Vera
37.1 Introduction 711
37.2 Pathomechanisms of Radiculopathy 713
37.3 Complex Spinal Pain Patient with Radiculopathy 715
37.4 Common Levels of Radiculopathy 716
37.4.1 Lumbar Radiculopathy 716
37.4.2 Cervical Radiculopathy 716
37.4.3 Thoracic Radiculopathy 718
37.5 Proposed Mechanisms of Laser Therapy on
Radiculopathy 721
37.6 Clinically Useful Treatment Protocols 723
37.6.1 Pulsed or Continuous Laser Therapy 723
37.6.2 Contact or Coupled Technique 725
37.6.3 Treatment of Associated Guarding Spasm 725
37.6.4 Treatment of Segmentally Innervated
Musculature 726
37.6.5 Treatment of L5 and S1 Radiculopathies 728
37.6.6 Treatment of C6 and C7 Radiculopathies 730
37.6.7 Treatment of Thoracic Radiculopathies 732
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38 Difficult Path to Treating Acute Ischemic Stroke Patients
with Transcranial Near-Infrared Laser Therapy 741
Paul A. Lapchak, Pramod Butte, and Padmesh S. Rajput
38.1 Introduction 742
38.2 NILT Penetration Profiles in Animals and Humans 743
38.3 Translational NILT Studies in Stroke Models 746
38.3.1 Is There a Correlation between NILT Power
Density and Improved Behavioral Function
in Animal Models? 746
38.4 NILT Safety Trials 749
38.5 NILT Stroke Clinical Trial Development 750
38.5.1 NEST-1 750
38.5.2 NEST-2 752
38.5.3 NEST-3 753
38.6 Need to Optimize NILT in a Standardized
Translational Model 753
38.7 Conclusion 754
39 Low-Level Laser (Light) Therapy for Rehabilitation in
Traumatic Brain Injury and Stroke, including Chronic
Aphasia 761
Margaret A. Naeser, Paula I. Martin, Michael D. Ho,
Maxine H. Krengel, Yelena Bogdanova, Jeffrey A. Knight,
Megan K. Yee, Ross Zafonte, Bang-Bon Koo, John G. Roubil,
and Michael R. Hamblin
39.1 Introduction 762
39.2 Mechanisms of LLLT 762
39.3 Traumatic Brain Injury 763
39.3.1 Introduction to TBI in Humans 763
39.3.2 Brain Imaging Studies in TBI 765
39.3.3 Cognitive Dysfunction in TBI 766
39.3.4 Poor Sleep in TBI 767
39.3.5 Pharmacologic Treatments for TBI 767
39.3.6 Cognitive Rehabilitation Therapies for TBI 768
39.3.7 Transcranial LED Treatments to Improve
Cognition and Sleep in Chronic mTBI 769
39.3.8 Intranasal LED Treatments to Improve
Cognition and Sleep in mTBI 771
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xxvi Contents
39.4 Stroke 773
39.4.1 Transcranial LLLT to Treat Acute Stroke 773 Transcranial LLLT studies to treat
acute stroke: Small-animal
studies 773 Transcranial LLLT to treat acute
stroke: Human studies 775
39.4.2 Transcranial LLLT to Treat Chronic Stroke 776 Transcranial LLLT to treat
chronic stroke: Human studies 776
39.4.3 Transcranial LLLT to Improve Language in
Chronic Aphasia Due to Stroke 778 Aphasia 778 Importance of specific LED
placement areas on the scalp to
treat aphasia in chronic stroke 779 Bilateral tLED treatment method 780 Left-hemisphere-only tLED
treatment method 781 Transcranial LLLT to treat
primary progressive aphasia,
neurodegenerative disease 783 Additional tLED treatment
studies with chronic aphasia due
to stroke 785
39.5 Other Noninvasive Brain Stimulation Therapies to
Treat TBI or Stroke 786
39.5.1 Transcranial Magnetic Brain Stimulation 786
39.5.2 Transcranial Direct Current Stimulation 788
39.6 Conclusion 791
40 Transcranial Near-Infrared Light for Major Depressive
Disorder: Targeting the Brain Metabolism 809
Paolo Cassano, Abigail R. Archibald, and Dan V. Iosifescu
40.1 Introduction 809
40.2 Transcranial Near-Infrared Light: Biological
Properties and Safety 810
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Contents xxvii
40.3 Depression, Antidepressant Treatment, and Brain
Energy Metabolism 812
40.4 Near-Infrared Light: Mood Effects in Healthy
Volunteers 813
40.5 Near-Infrared Light: Effect on Mood in TBI and
PTSD Patients 814
40.6 Near-Infrared Light For Depression 816
40.6.1 Near-Infrared Light for Depression and
Anxiety: Single Session 816
40.6.2 Near-Infrared Light for Depression:
Multiple Sessions 817
40.6.3 Near-Infrared Light for Depression:
Multiple Sessions and Pulse Light 818
40.7 Conclusion 819
41 Low-Level Laser Therapy: A Corner Stone in the
Management of Cancer Therapy–Induced Mucositis 825
Ren ´
e-Jean Bensadoun, Idriss Troussier, and Raj G. Nair
41.1 Introduction 825
41.2 What is Mucositis? 826
41.3 Low-Level Laser Therapy 826
41.4 Clinical Trials 827
41.5 Recommendations and Future Directions 829
41.6 Conclusion 829
42 Photobiomodulation in Dentistry: Manipulating
Biostimulation and Bioinhibition for Clinical Success 833
Gerry Ross and Alana Ross
42.1 Introduction 834
42.1.1 Keys to Successful Use of PBM in Dentistry 835
42.1.2 Determining the Appropriate Dose 835
42.2 Dental Procedures Using Laser Therapy 837
42.2.1 Surgical Extractions 837
42.2.2 Alveolar Osteitis (Dry Socket) 839
42.2.3 Dental Infection 839
42.2.4 Restorations 841 Cementing crowns 843
42.2.5 Nausea and Gagging 843
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xxviii Contents
42.2.6 Dentin Hypersensitivity 844
42.2.7 Soft Tissue Lesions 846 Herpes lesions 847 Aphthous ulcers 848 Appliance irritation mucosal
lesions 849
42.2.8 Oral Mucositis 849
42.2.9 Gingivitis 850
42.2.10 Periodontitis 851
42.2.11 Endodontics 852 Pulpotomies 852
42.2.12 Nerve Regeneration 852
42.2.13 Orthodontics 854
42.2.14 Implants 855
42.2.15 Sinusitis 857
42.2.16 Temporomandibular Joint Pain 857
42.3 Conclusion 860
43 Photobiomodulation for the Clinical Treatment of
Age-Related Macular Degeneration 867
Graham Merry and Robert Dotson
44 Laser (Light) Therapy for Postherpetic Neuralgia 891
Kevin C. Moore and R. Glen Calderhead
44.1 Overview of Postherpetic Neuralgia 891
44.1.1 Aetiology 891
44.1.2 Incidence 892
44.1.3 Signs and Symptoms 892
44.1.4 Treatment Options 893
44.1.5 Prognosis 893
44.2 Laser (Light) Therapy 893
44.2.1 History 893
44.2.2 Clinical Research 895
44.2.3 Mechanisms of Action of LLLT 897
44.3 Enter the Light-Emitting Diode 898
44.3.1 Background 898
44.3.2 The “NASA LED” 898
44.3.3 Efficacy of LED Sources 900
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Contents xxix
44.3.4 Clinical Evidence 900
44.4 Conclusion 902
45 Laser Acupuncture 907
Lucas F. de Freitas and Michael R. Hamblin
45.1 Introduction 908
45.2 Laser Acupuncture in Pain Reduction 911
45.3 Laser Acupuncture in Wound Healing 914
45.4 Laser Acupuncture in Respiratory Diseases 915
45.5 Laser Acupuncture in Heart Rate and Heart Rate
Variation 915
45.6 Laser Acupuncture and Brain Activity 917
45.7 Auricular Laser Acupuncture 922
45.8 Other Applications for Laser Acupuncture 923
45.9 Conclusion 927
46 Intravascular Laser Irradiation of Blood 933
Daiane Thais Meneguzzo, Leila Soares Ferreira,
Eduardo Machado de Carvalho,
and C´
assia Fukuda Nakashima
46.1 Introduction 933
46.2 History of ILIB 934
46.3 Antioxidant Action of ILIB 936
46.4 Modified ILIB Techniques 943
46.4.1 Intranasal Irradiation 944
46.4.2 Wrist Skin Irradiation 945
46.5 Side Effects and Contraindications of ILIB 946
47 Nonsurgical Laser Therapy for Type 1 and Type 2 Diabetes 953
Leonardo Longo
47.1 Epidemiology 953
47.2 History 955
47.3 Background and Objectives 959
47.4 Study Design 961
47.5 Results and Discussion 967
47.6 Conclusion 972
48 Laser Therapy of Traumatic Central Nervous System Injuries 977
Leonardo Longo and Diego Longo
48.1 State of the Art and Objectives 977
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xxx Contents
48.2 Study Design and Methodology 979
48.3 Results and Discussion 984
48.4 Conclusion 986
49 Low-Level Laser (Light) Therapy: Aesthetic Applications for
Hair 989
Felipe Scholz Ramos, Andr´
e Luiz de Oliveira Ramos,
and Marcelo Victor Pires de Sousa
49.1 Physiology of Hair Growth (Phases) 990
49.2 Types of Hair Loss and Some Treatments 993
49.2.1 Androgenetic Alopecia 993
49.2.2 Alopecia Areata 994
49.2.3 Chemotherapy-Induced Alopecia 995
49.2.4 Telogen Effluvium 995
49.2.5 Scarring Alopecia 996
49.3 Treatments 996
49.3.1 Finasteride 997
49.3.2 Minoxidil 997
49.4 In Vivo Studies of LLLT 998
49.5 LLLT for Hair Growth: Clinical Trials 1000
49.6 LLLT for Hair Growth and Hair Loss
(Proposed Mechanisms) 1003
49.7 Phototherapy Devices for Hair Aesthetics 1008
49.8 Future Perspectives 1011
49.9 Glossary 1011
50 Low-Level Laser (Light) Therapy for Cosmetics and
Dermatology 1017
Mossum K. Sawhney and Michael R. Hamblin
50.1 Introduction 1017
50.2 LLLT in Dermatology 1018
50.2.1 LLLT for Skin Rejuvenation 1018
50.2.2 LLLT for Acne 1023
50.2.3 LLLT for Photoprotection 1026
50.2.4 LLLT for Herpes Virus 1028
50.2.5 LLLT for Vitiligo 1030
50.2.6 LLLT for Reduction of Pigmented Lesions 1032
50.2.7 LLLT for Hypertrophic Scars and Keloids 1033
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Contents xxxi
50.2.8 LLLT for Healing of Burns 1035
50.2.9 LLLT for Psoriasis 1037
50.3 Conclusion 1039
51 Low-Level Laser Therapy for Body Contouring and Fat
Reduction 1049
Gaurav K. Gupta
51.1 Background 1049
51.2 LLLT in Lipoplasty 1050
51.3 LLLT in Cellulite Treatment 1052
51.4 LLLT Mechanism of Action 1053
51.5 Future Directions 1054
52 Transcranial Low-Level Laser (Light) Therapy for
Neurocognitive Enhancement 1057
Julio C. Rojas and F. Gonzalez-Lima
52.1 Introduction 1057
52.2 Primary LLLT Neurochemical Effects: Cytochrome
Oxidase Effects on Oxygen and Nitric Oxide 1058
52.3 Secondary LLLT Neurobiological Effects:
Cytochrome Oxidase Induction and Cerebral
Hemodynamic Response 1060
52.4 Brain Network Mechanisms of LLLT Relevant to
Cognitive Function 1063
52.5 Dosimetry Parameters Relevant for Transcranial
LLLT and Cognitive Enhancement 1065
52.6 Cognitive Effects of Transcranial LLLT 1068
52.7 Conclusion 1071
53 Post-Operative Uses of Low-Level Laser Therapy 1077
Maria Cristina Chavantes, Nathali Cordeiro Pinto, and
Vanessa Milanesi Holanda
53.1 LLLT in Post-Cardiovascular Surgery 1078
53.1.1 LLLT in Thoracic-Cardiovascular Surgery 1081
53.2 LLLT in Neurosurgery Procedures 1082
53.2.1 Stroke 1082
53.2.2 Pain 1083
53.2.3 Spinal Cord: Trauma and Pain Problems 1083
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xxxii Contents
53.2.4 Application of LLLT in Pediatric and Adult
Neurosurgical Procedures 1084
53.2.5 LLLT in Neurosurgery Procedures 1087
53.3 Final Remarks on Post-Operative Surgeries 1089
54 Bright New World: Future Directions of Low-Level Laser
(Light) Therapy 1093
Marcelo Victor Pires de Sousa and Maria Cristina Chavantes
54.1 Introduction 1094
54.2 New Clinical Indications for LLLT 1094
54.2.1 Stem Cells 1095
54.2.2 Transcranial LLLT for Brain Disorders 1096
54.2.3 Ophthalmology 1097
54.2.4 Autoimmune Diseases 1098
54.2.5 Lung Disease and Tracheal Stenosis 1098
54.2.6 Hemodynamic Effect 1099
54.2.7 Performance Enhancement 1099
54.2.8 Optimizing Treatment 1100
54.3 Novel Light Sources for LLLT 1100
54.3.1 Wearable LLLT Devices: Bandages and
Clothing 1101
54.3.2 Implantable LEDs for Brain and Spine 1102
54.3.3 Swallowable LED Source Capsule 1102
54.4 A Bright New World with Photobiomodulation 1103
Index 1107
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Low-level laser (light) therapy (LLLT) has in recent years become
one of the fastest growing fields of medicine. Originally considered
to be firmly and enduringly sequestered in the arena of “alternative
and complementary medicine”, LLLT has staged something of a
breakout. The reasons for this remarkable change in perception by
both the medical profession and the general public are interesting to
Firstly we have the substantial advances in knowledge that
have been made in understanding the underlying mechanisms
of action. No longer do we have to rely on hand-waving and
vague comments about the cells “feeding on light” in an analogous
manner to photosynthesis in the plant kingdom. Now we understand
many of the molecular mechanisms of photon absorption, we
know which subcellular organelles respond to light, and appreciate
some of the signaling pathways and transcription factors that are
activated, and the tissue responses that occur including activation
and mobilization of stem cells.
The second big sea change has been the realization that we do not
necessarily need lasers to carry out LLLT. In the old days much laser
therapy was carried out by “practitioners” and therapists of various
types and was considered to be a specialty for which significant
training was required. This was reasonable in light of the real
concerns for laser eye safety and protecting against other possible
hazards. Now, however, the use of light-emitting diode (LED) arrays
is rapidly taking off, and these devices are readily available on
online shopping websites and are also sold on late-night television.
Although some knowledge is still required to understand the best
parameters to use for each different indication, and which can be
July 16, 2016 11:1 PSP Book - 9in x 6in 00-Hamblin-prelims
xxxiv Preface
achieved relatively easily considering the broad dissemination of
information over the Internet.
Thirdly we have the growing realization that LLLT has a broad
range of systemic and regional effects in addition to the local effects
that were initially the main focus of everyone’s attention. Since LED
arrays by definition have a broad area illumination spot, significant
amounts of tissue are exposed to light, and light is absorbed by blood
flowing within the skin and other tissues that are exposed to light.
Light can be applied to nerves and lymph nodes to give regional
effects, as well as to the actual lesion that is being treated.
Fourthly we have seen an impressive increase in the number
of applications of LLLT to the brain. LLLT was originally tested as
a treatment for acute ischemic stroke and has been used for the
same over the last ten years. However, now its sphere has widened
and is being applied to other instances of brain trauma including
chronic stroke, acute traumatic brain injury (TBI), and chronic
TBI. A number of chronic neurodegenerative diseases including
Alzheimer’s disease and Parkinson’s disease have shown to be
benefited by LLLT. A wide range of psychiatric disorders including
depression, anxiety, post-traumatic stress disorder, and autism
spectrum disorder have been found to be susceptible to treatment
with LLLT.
Fifthly we are beginning to see significant progress in the use
of LLLT for enhancement of performance in normal people. The
most developed area of this application is the enhancement of
muscle performance in athletes and competitors in a wide range
of sports. Not only can LLLT increase the amount of work and
power that can be produced by muscles, but it can also increase the
speed of recovery after exercise and can be a great help in training
regimens. A less developed area is that of enhancement of cognitive
performance, and improvement in memory and mood using LLLT.
We expect that efforts toward realizing these goals will be emerging
Lastly, but worth mentioning, is the use of LLLT for cosmetic
and aesthetic improvements. Stimulation of hair regrowth is now
well established, and improvement of fine lines and wrinkles in
the face is also growing in popularity. The use of LLLT to combat
one of the biggest problems in the modern age, obesity and excess
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Preface xxxv
fat deposits is also starting to take off. These applications address
many of the issues driving the home-use market for LLLT devices, as
consumers are generally prepared to spend their disposable income
on aesthetic improvements.
This handbook represents the most comprehensive edited book in
the field of LLLT [now called photobiomodulation (PBM) therapy]
that has been published to date. With 54 chapters spread over more
than 1100 pages it provides broad coverage of all the multitudinous
topics that comprise this most fascinating of medical therapies. The
reader will find chapters on the basic principles, mechanisms of
action, dosimetry, devices, in vitro studies, a large range of animal
models, clinical applications in veterinary medicine, and broad
coverage of a wide range of human clinical studies and uses. We
expect it to become the gold-standard reference book for some
considerable time to come.
Michael R. Hamblin
Marcelo Victor Pires de Sousa
Tanupriya Agrawal
Summer 2016
July 16, 2016 11:1 PSP Book - 9in x 6in 00-Hamblin-prelims
... [27]) Together, these mechanisms substantiate one basic premise: that external electromagnetic energy supplementation can enhance and even substitute for endogenous ATP to power and modulate physiologically reparative and regenerative mechanisms that can help reestablish homeostasishomeokinesis , even when metabolic pathways have been compromised [10,25,26,27,28,30,31] 2. Selective, non-invasive, long-range, external energy supplementation is based on the idea that physiologic processes (fluctuations and/or oscillations) can be activated and synchronized through the body's preeminent medium, water, CO 2 and membrane receptors. While a full elucidation of these ideas can be found elsewhere [29], it is worth reviewing some of its bases [25,32,33]. According to the Stark–Einstein law, only absorbed light can trigger photochemical change [32]. ...
... While a full elucidation of these ideas can be found elsewhere [29], it is worth reviewing some of its bases [25,32,33]. According to the Stark–Einstein law, only absorbed light can trigger photochemical change [32]. At less than 1100 nm, the absorption coefficient (AC) of water is low [34]. ...
... In materials with a low AC, light propagates with little attenuation. Hence, pulses as short as 60 fsec with a center wavelength of 800 nm can propagate through as much as 6 m of water [26,32,35,36]. Despite its low AC in the 600-1100 nm range, water is a major biologic photoacceptor for several reasons. ...
Full-text available
The roles of water and carbon dioxide in laser/light interactions in higher-order biological systems and their implications in cellular microenvironments and complex systemic processes for the restoration of homeostasis-homeokinesis, even when metabolic pathways have been compromised, are discussed. This lecture summarizes three decades of pre-clinical and clinical investigations and the basis for a potentially new therapeutic approach for the treatment of advanced cancer and other complex diseases using laser photobiomodulation. We propose that light-water interactions offer a potent, alternate and complementary pathway to activate and modulate tumor suppression and/or proto-oncogenic expression through energy transfer via water and CO 2 in multi-fractal regimes, leading to the coupling of spatiotemporal oscillators. Laser photobiomodulation may, thus, offer the possibility of targeting multiple hallmarks of cancer and other complex diseases using fit-for-purpose electromagnetic (light) energy to restore physiologically reparative and regenerative mechanisms that can help reestablish homeostasis-homeokinesis, constituting a new emerging paradigm in the treatment of cancer and other complex diseases.
... Moreover, the human body can be in resonance while energy is transferred among different modes or trajectories, magnifying energy absorption and transport due to its multi-fractal architecture. 25 Differences in oxidation-reduction (redox) potential between degrading and well-oxygenated tissues translate into significant injury potentials. This allows diseased tissues to be selectively targeted in accord with the extension of second law of thermodynamics and Onsager's theory of reciprocal relations. ...
Full-text available
Objective: To highlight future potential roles of photobiomodulation (PBM) in light of recent discoveries of the molecular mechanics of the biological clock (BC). Background: The 2017 Nobel Prize in Physiology or Medicine is awarded to JC Hall, M Rosbash and MW Young for their discoveries on the molecular mechanisms controlling the circadian rhythm. Concurrently, discoveries in the interaction of the light / water interface in simple and complex biological systems are contributing to the understanding of human physiology and its role in the synchronization of physiological rhythms (PR). Method: Perspective Results: An anatomical and functional description of the BC is presented in light of current findings. Examples of synchronization of deregulated PRs in patients with geographic atrophy-Age Related Macular Degeneration, (ga-AMD), and Alzheimer's disease (AD) treated with PBM-T are referred. The mechanism by which PBM acts on the interaction of the light / water interface to regulate PR is also discussed. Conclusion: This paper explores the importance of PR, the negative connotations of their deregulation, as well as the means by which PBM may be able to help power and restore altered PRs to reestablish homeostasis / homeokinesis in higher biological systems.
Full-text available
Background: Under physiological conditions, endothelial cells are the main regulator of arterial tone homeostasis and vascular growth, sensing and transducing signals between tissue and blood. Disease risk factors can lead to their unbalanced homeostasis, known as endothelial dysfunction. Red and near-infrared light can interact with animal cells and modulate their metabolism upon interaction with mitochondria's cytochromes, which leads to increased oxygen consumption, ATP production and ROS, as well as to regulate NO release and intracellular Ca2+ concentration. This medical subject is known as photobiomodulation (PBM). We present a review of the literature on the in vitro and in vivo effects of PBM on endothelial dysfunction. Methods: A search strategy was developed consistent with the PRISMA statement. The PubMed, Scopus, Cochrane, and Scholar electronic databases were consulted to search for in vitro and in vivo studies. Results: Fifty out of >12,000 articles were selected. Conclusions: The PBM can modulate endothelial dysfunction, improving inflammation, angiogenesis, and vasodilatation. Among the studies, 808 nm and 18 J (0.2 W, 2.05 cm2) intracoronary irradiation can prevent restenosis as well as 645 nm and 20 J (0.25 W, 2 cm2) can stimulate angiogenesis. PBM can also support hypertension cure. However, more extensive randomised controlled trials are necessary.
After 50 years of studies on photobiomodulation (PBM) there is still so much to investigate to understand the laser‐light – non‐plant cells interactions. The current scientific knowledge allows to say that the phenomena induced by PBM are based on cellular pathways that are key points of cell life. The mitochondria chromophores, also present on the bacterial membrane, the calcium channels, ion that regulates the life‐and‐death cellular processes, as well as the TRP‐family, whose genes have been found in protozoa and suggest that its basic mechanism evolved long before the appearance of animals, seem to be elective targets in photobiomodulatory events by wavelengths from 600 nm up to 980 nm. The ambiguous resulting cellular communication way, mediated by ATP, ROS and/or calcium leads to cell manipulation, which modifies its metabolism and whose response connects all life‐forms from bacteria to vertebrates. Because of the Giano‐Bifronte features of ROS and calcium, as well as the fine balance of energetic mitochondrial processes, whose alteration is responsible of several diseases, the PBM can show unpredictable results and it requires scrupulous approach to avoid cellular damages. However, when carefully applied PBM is able to improve non‐healthy cell's responses and represents a reliable support in human and veterinary medicine. This article is protected by copyright. All rights reserved.
Full-text available
“Real” liquid aqueous systems general- ly represent complex systems where the phase of polarized water, as recently pro- pounded by Pollack in his description of “exclusion zone” water, contrasts with the coexisting, but much less well organized, bulk water. Polarized water is a potential electron donor (i.e., reducer). Under con- ditions where electrons may be donated to dissolved oxygen, the process is one of “slow water burning,” equivalent to “water respiration.” When carbon dioxide and ni- trogen are present, free energy released in the course of this “respiration” can be used for performing (chemical) work, leading to the production of organic compounds, and further complicating the system as a whole. The same conclusions follow from the theo- ry of coherent water based on the principles of quantum electrodynamics. Such dynamic systems meet the requirements of the “liv- ing state” based on the general theory of living matter formulated by Bauer.
Full-text available
In its concern with ‘success’ or ‘failure’, retrospective history of science sometimes fails to display to us the historical integrity of a particular science in its own time. The neglect of the history of the colloid-orientated biochemistry of 60 years ago is probably due to an understandable preoccupation with the success of metabolic biochemistry. But it demonstrates a lack of sympathy for our predecessors' problems; problems that they grappled with and sometimes failed to solve. In its emphasis on the links between structure and function at the level of the biological molecule, colloid biochemistry highlighted an important problem that was seldom at the forefront of research on metabolism. The molecular chemistry of the modern period has resulted from an integration of both approaches into a coherent whole.
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We here examine the putative first step in the origin of life: the coalescence of dispersed molecules into a more condensed, organized state. Fresh evidence implies that the driving energy for this coalescence may come in a manner more direct than previously thought. The sun's radiant energy separates charge in water, and this free charge demonstrably induces condensation. This condensation mechanism puts water as a central protagonist in life rather than as an incidental participant, and thereby helps explain why life requires water.
The last decade has seen a transformation in understanding of the role of membrane-bound interfacial water. Whereas until recently water was treated principally as a continuum (primarily screening charges of lipids and proteins), it has become apparent recently that consideration of water’s molecular-level properties is critical in understanding a variety of biochemical and biophysical processes. Here we investigate the structure and dynamics of water in contact with a monolayer of artificial lung surfactant, composed of four types of lipids and one protein. We probe this water using frequency-domain sum-frequency generation (SFG) spectroscopy, and a newly developed time-domain, three-pulse technique, in which the vibrational relaxation of interfacial water molecules is followed in real time. We characterize interfacial water in three systems: a monolayer of the pure lipid that is the majority of the lung surfactant mixture, a monolayer of the four lipids constituting the mixture, and a monolayer of the four lipids and the protein. We find subtle differences in the water structure and dynamics that depend on the mixture density and composition. In particular, frequency-domain measurements suggest that in the lipid mixture and the lipid mixture + protein, the relatively bulky lipids (those that have either three or unsaturated hydrocarbon tails) tend to be squeezed out at higher pressure. Measurements using the time-domain, three-pulse technique make clear that structural relaxation of interfacial water is significantly slowed down upon adding small amounts of protein to the lipids. Both results are consistent with prior measurements using other techniques in which more fluid lipids were shownto be ‘squeezed out’ of lung surfactant at high compression and the role of protein in the mixture was demonstrated to be a catalyst for the formation of multilayers under compression that are subsequently reintegrated into the monolayer on expansion.
The molecule ATP, famous as an essential energy source inside cells, also carries critical messages between cells. That dual role is suggesting fresh ideas for fighting human diseases
While recent research on interfacial water has focused mainly on the few interfacial layers adjacent to the solid boundary, century-old studies have extensively shown that macroscopic domains of liquids near interfaces acquire features different from the bulk. Interest in these long-range effects has been rekindled by recent observations showing that colloidal and molecular solutes are excluded from extensive regions next to many hydrophilic surfaces [Zheng and Pollack Phys. Rev. E 2003, 68, 031408]. Studies of these aqueous "exclusion zones" reveal a more ordered phase than bulk water, with local charge separation between the exclusion zones and the regions beyond [Zheng et al. Colloid Interface Sci. 2006, 127, 19; Zheng and Pollack Water and the Cell: Solute exclusion and potential distribution near hydrophilic surfaces; Springer: Netherlands, 2006; pp 165-174], here confirmed using pH measurements. The main question, however, is where the energy for building these charged, low-entropy zones might come from. It is shown that radiant energy profoundly expands these zones in a reversible, wavelength-dependent manner. It appears that incident radiant energy may be stored in the water as entropy loss and charge separation.
P2X and P2Y nucleotide receptors are described on sensory neurons and their peripheral and central terminals in dorsal root, nodose, trigeminal, petrosal, retinal and enteric ganglia. Peripheral terminals are activated by ATP released from local cells by mechanical deformation, hypoxia or various local agents in the carotid body, lung, gut, bladder, inner ear, eye, nasal organ, taste buds, skin, muscle and joints mediating reflex responses and nociception. Purinergic receptors on fibres in the dorsal spinal cord and brain stem are involved in reflex control of visceral and cardiovascular activity, as well as relaying nociceptive impulses to pain centres. Purinergic mechanisms are enhanced in inflammatory conditions and may be involved in migraine, pain, diseases of the special senses, bladder and gut, and the possibility that they are also implicated in arthritis, respiratory disorders and some central nervous system disorders is discussed. Finally, the development and evolution of purinergic sensory mechanisms are considered.
Previous work from this and other laboratories has demonstrated large pH gradients in water. Established by passing current between immersed electrodes, pH gradients between electrodes were found to disappear slowly, persisting for tens of minutes after the current had been turned off. We find here that these pH gradients reflect a genuine separation of charge: at times well after disconnection of the power supply, current could be drawn through a resistor placed between the charging electrodes or between pairs of electrodes positioned on either side of the midline between original electrodes. In some experiments, it was possible to recover the majority of charge that had been imparted to the water. It appears, then, that water has the capacity to store and release substantial amounts of charge.