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Assessment and Multimodal
Management of Pain
AN INTEGRATIVE APPROACH
This page intentionally left blank
We would like to dedicate this work to all people who experience pain and the clinicians
who care for them; and to all who have contributed to the field of pain management
through their passion and tireless efforts in research, education, leadership, and advocacy.
viii Reviewers
Meera K. Shah, PharmD, AAHIVP Linda Wilson, PhD, RN, CPAN, CAPA, BC, CNE, CHSE,
Clinical Pharmacist CHSE-A, ANEF, FAAN
Hepatology and Infectious Disease Assistant Dean for Special Projects, Simulation and CNE
University of Kansas Health Systems Accreditation
Kansas City, Kansas College of Nursing and Health Professions
Drexel University
Tara C. Shaw, RN, MSN Philadelphia, Pennsylvania
Assistant Professor
Nursing Robin Ye
Goldfarb School of Nursing at Barnes Jewish College Registered Pharmacist–State of Illinois
St. Louis, Missouri Doctor of Pharmacy (PharmD)
Board Certified Pharmacotherapy Specialist (BCPS); Basic
Paula Denise Silver, BS Biology, PharmD Life Support (BLS)
Medical Instructor Clinical Pharmacist
Medical Assisting/LPN/RN Inpatient Pharmacy
ECPI University: School of Health Science NorthShore University HealthSystem–Glenbrook Hospital
Newport News, Virginia Glenview, Illinois
x Contributors
Adjunct Associate Professor of Pharmacy Practice & Pain Mena Raouf, PharmD, BCPS
Management Clinical Pharmacy Programs Coordinator–Pain
Albany College of Pharmacy & Health Sciences Management
Albany, New York Kaiser Permanente
Federal Way, Washington
Carla R. Jungquist, PhD, ANP-BC, FAAN
Assistant Professor Nitin K. Sekhri, MD
School of Nursing Medical Director of Pain Management
University at Buffalo Anesthesiology
Buffalo, New York Westchester Medical Center
Valhalla, New York
Courtney Kominek, PharmD Assistant Professor
Clinical Pharmacy Specialist-Pain Management Anesthesiology
Pharmacy New York Medical College
Harry S. Truman Memorial Veterans’ Hospital Valhalla, New York
Columbia, Missouri
Erica L. Wegrzyn, BS, PharmD
Susan O’Conner-Von, PhD, RN-BC, CHPPN, CNE Clinical Pharmacy Specialist, Pain Management
Associate Professor Stratton VA Medical Center
School of Nursing Albany, New York
University of Minnesota Adjunct Faculty
Minneapolis, Minnesota Western New England University College of Pharmacy
Director of Graduate Studies Springfield, Massachusetts
Center for Spirituality and Healing Albany College of Pharmacy & Health Sciences
University of Minnesota Albany, New York
Minneapolis, Minnesota
Elsa Wuhrman, DNP, FNP,BC
Shalvi B. Parikh, MBBS Nurse Practitioner and Assistant Professor of Nursing at
Former Research Assistant CUIMC
Department of Anesthesia Pain Management/Anesthesiology
Division of Pain Medicine Columbia University Irving Medical Center
Westchester Medical Center New York, New York
Valhalla, New York
Christine Peltier, DNP, RN-BC, FNP-BC Clinical Scenario Contributors

Nurse Practitioner
M-Health, Fairview Cindy Kerwick
Minneapolis, Minnesota
Denise Kuhn
Thien C. Pham, AS, BS, PharmD
Clinical Pharmacy Specialist-Pain Management Brian Quinlan
Pharmacy
VA Long Beach Healthcare System
Long Beach, California
Eva Pittman, MSN, RN-BC

LEAN Strategies Coach
LEAN Strategies Department
New Hanover Regional Medical Center
Wilmington, North Carolina
xvi Contents
7 Pain Assessment of Patients Who Cannot 11 Opioid Analgesics, 222

Self-Report Pain, 120 Maureen F. Cooney, Mena Raouf, Jeffrey J. Bettinger,
Debra Drew and Ann Quinlan-Colwell Erica L. Wegrzyn, and Jeffrey Fudin
Pain Assessment of Patients Who Cannot Self-Report Section 1, 223
Pain, 120 Opioid Pharmacology, 223
Pain Assessment in Critically Ill Adults Who Cannot Opioid Receptors, 224
Self-Report Pain, 124 Factors Affecting Drug Response, 226
Patients With Delirium Who Cannot Opioid Classes, 232
Self-Report Pain, 125 Key Points, 236
Patients With Dementia Who Cannot Section 2, 236
Self-Report Pain, 125 Opioid Selection, 236
The Checklist of Nonverbal Pain Indicators Key Points, 269
(CNPI), 129 Section 3, 269
Patients With Intellectual Disabilities Who Cannot Opioid Dosing Practices, 269
Self-Report Pain, 129 Tapering and Discontinuing Opioid Therapy, 287
Patients at the End of Life Who Cannot Self-Report Key Points, 289
Pain, 131 Case Scenario, 289
Newer Trends in Pain Assessment for Patients Who References, 291
Cannot Self-Report Pain, 131
Cautions, 132 12 Common Unintended Effects of Opioids, 303
Key Points, 132 Ann Quinlan-Colwell and Maureen F. Cooney
Case Scenario, 132 Constipation, 306
References, 133 Xerostomia (Dry Mouth), 311
Opioid-Induced Nausea and Vomiting, 312
8 Assessment of Factors Affecting Pain and Pruritus, 314
Affected by Pain, 136 Urinary Retention, 319
Ann Quinlan-Colwell Hypogonadism, 321
Sedation, 323
Sleep, 136
Myoclonus, 325
Anxiety and Depression, 146
Opioid-Induced Hyperalgesia, 326
Family Assessment, 158
Physical Dependence on Opioids, 327
Financial Assessment, 158
Opioid Tolerance, 328
Key Points, 158
Immune Suppressing Effect of Opioids, 328
Case Scenario, 159
Key Points, 329
References, 159
Case Scenario, 329
9 Basic Concepts Involved with Administration References, 329
of Analgesic Medications, 163 13 Preventing Opioid-Induced Advancing
Maureen F. Cooney and Ann Quinlan-Colwell Sedation and Respiratory Depression, 337
Patient Considerations, 163 Carla R. Jungquist and Ann Quinlan-Colwell
Route Selection, 167
Opioids and Respiratory Function, 338
Analgesic Dosing Considerations, 181
Advancing Sedation and Opioid-Induced Respiratory
Key Points, 190
Depression, 338
Case Scenario, 191
Identification of the Risk Factors, 339
References, 191
Associated Pharmacologic Factors, 342
Strategizing to Improve Safety for Patients at Risk, 347
10 Nonopioid Analgesic Medications, 195
Assessing the Patient for Risk, 347
Meredith W. Crumb, Timothy J. Atkinson, and Procedures for Intermittent Nursing Assessment for All
Maureen F. Cooney Patients on Opioids: Level of Sedation, 348
Aspirin and Nonsteroidal Antiinflammatory Procedures for Intermittent Nursing Assessment for All
Drugs, 195 Patients on Opioids: Respiratory Status, 351
Multimodal Use of Nonopioid Analgesics, 214 Interventions After Assessment, 353
Key Points, 215 Summary, 353
Case Scenario, 215 Key Points, 353
References, 216 Case Scenario, 354
Contents xvii
Acknowledgments, 354 18 Regional Analgesia, Local Infiltration, and Pain

References, 354 Management, 474
14 Opioid Use Disorder, 360 Maureen F. Cooney, Christine Peltier, and Ann
Ann Quinlan-Colwell and Maureen F. Cooney Quinlan-Colwell
Substance Use Disorder and Opioid Use Disorder, 361 Neuraxial Analgesia, 475
Caring for Patients With Pain and Opioid Use Regional Analgesia, 510
Disorder, 363 Regional Analgesia Infusion Systems, 518
Treatment of Opioid Use Disorder, 365 Local Infiltration Analgesia, 520
Pain and Opioid Use Disorder: Acute Care Setting, 369 Additional Analgesic Procedures Involving Use of Local
Strategies to Reduce Risk, 376 Anesthetics, 524
Key Points, 377 Key Points, 525
Case Scenario, 379 Case Scenario, 526
References, 379 References, 526
15 Coanalgesic Medications, 384 19 Interventional Approaches, 533

Courtney Kominek and Maureen F. Cooney Nitin K. Sekhri, Emily Davis, Ann Quinlan-Colwell, and
Maureen F. Cooney
Medication Selection, 386
Gabapentinoids, 389 Anatomy of the Central Nervous System, 533
Antidepressants, 394 Spinal Pain, 533
Alpha-Adrenergic Receptor Agonists, 398 Diagnostic Imaging, 537
Corticosteroids, 401 Spinal Injections, 538
N-Methyl-d-Aspartate Receptor Antagonists, 403 Implantable Therapies, 543
Sodium Channel Blockers: Lidocaine and Mexiletine, 409 Key Points, 554
Muscle Relaxants, 412 Case Scenario, 554
Dronabinol, Nabilone, and Cannabidiol, 416 Acknowledgement, 555
Other Coanalgesic Medications, 418 References, 555
Key Points, 418 20 Exercise and Movement, 560
Case Scenario, 419
References, 419 Ann Quinlan-Colwell
Fear of Pain With Movement, 561
16 Topical Analgesics for the Management of Exercise-Induced Hypoalgesia, 564
Acute and Chronic Pain, 429 Movement, 564
Elsa Wuhrman, Maureen F. Cooney, and Thien C. Pham Dance Movement Therapy, 565
Benefits of Topical Analgesics, 429 Exercise, 566
Types of Topical Analgesics, 431 Tai Chi, 569
Compound Analgesics, 441 Yoga, 570
Key Points, 443 Physical Therapy, 571
Case Scenario, 443 Patient Education for All Exercise and Movement, 576
References, 444 Key Points, 576
Case Scenario, 576
17 Patient-Controlled Analgesia, 447 References, 578
Ann Quinlan-Colwell
21 Distraction and Relaxation, 586
General Concepts, 447
Optimize Safety Within the Patient-Controlled Michele Erich, Ann Quinlan-Colwell, and
Analgesia Process, 449 Susan O’Conner-Von
Prescription Components, 455 Distraction, 586
Routes of Administration, 458 Relaxation, 591
Patient Assessment and Monitoring to Optimize Progressive Muscle Relaxation, 594
Safety, 462 Music Therapy, 596
Evaluating Equipment to Optimize Patient Animal-Assisted Therapy, 600
Safety, 464 Guided Imagery, 603
Authorized Agent–Controlled Analgesia, 465 Autogenic Training, 604
Key Points, 468 Key Points, 605
Case Scenario, 468 Case Scenario, 605
References, 468 References, 606
xviii Contents
22 Cognitive-Behavioral and Psychotherapeutic 25 Spirituality as a Component of Multimodal

Interventions as Components of Multimodal Pain Management, 673
Analgesic Pain Management, 613 Susan O’Conner-Von and Ann Quinlan-Colwell
Geralyn Datz and Ann Quinlan-Colwell Spirituality, 673
Integrative, Interdisciplinary, and Multimodal Pain Prayer, 674
Treatment, 613 Meditation, 675
Interdisciplinary Pain Rehabilitation or Functional General Cautions and Precautions Regarding
Restoration Programs, 615 Meditation, 682
Cognitive-Behavioral Therapy, 617 Key Points, 683
Evidence Supporting Cognitive-Behavioral Therapy for Case Scenario, 683
Pain Management, 622 References, 684
The Activating Event Belief Consequence Model, 624
26 Natural Products: Supplements, Botanicals,
Acceptance and Commitment Therapy, 625
Biofeedback (Applied Psychophysiology), 626 Vitamins, and Minerals as a Component of
Mindfulness-Based Stress Management and Multimodal Pain Management, 687
Mindfulness-Based Cognitive Therapy, 627 Ann Quinlan-Colwell
Psychoeducation, 630 Dietary Supplements, 688
Key Points, 631 Botanicals and Herbs, 688
Case Scenario, 631 Pharmaconutrients: Nutritional Modulators
References, 631 of Pain, 702
Supplements, 707
23 Energy Healing Therapies or Vitamins, 716
Biofield Therapies as Components of Key Points, 723
Multimodal Analgesic Pain Management, 636 Case Scenario, 723
Ann Quinlan-Colwell and Susan O’Conner-Von References, 723
Reiki, 637 27 Additional Nonpharmacologic Interventions
Therapeutic Touch, 638
as Components of Multimodal Pain
Healing Touch, 642
Acupuncture, 642 Management, 738
Auricular Acupuncture, 644 Ann Quinlan-Colwell
Acupressure, 647 Aromatherapy, 739
Key Points, 648 Caring, Empathy, and Compassion by Caregivers, 742
Case Scenario, 648 Crossing Hands and/or Arms Over the Midline, 743
References, 648 Dietary Choices, 745
Environmental Modifications, 747
24 Manual Therapies for Pain Hypnosis, 749
Management, 652 Mirror Therapy or Mirror Visual Feedback Therapy, 751
Ann Quinlan-Colwell Obesity and Weight Management, 754
Manual Therapy, 652 Static Magnet Therapy, 756
Osteopathy, Osteopathy Manual Medicine, or Temperature Modalities, 756
Osteopathic Manipulative Therapy, 653 Alternating or Contrasting Temperature Therapy, 759
Craniosacral Therapy, 654 Valsalva Maneuver, 760
Massage Therapy, 655 Key Points, 761
Reflexology, 659 Case Scenario, 761
Chiropractic Practice, 664 References, 762
Myofascial Trigger Point Therapy, 666 28 Improving Institutional Commitment for
Muscle Energy Technique, 667
Effective Multimodal Pain Management, 770
Fascial Distortion Model, 667
Key Points, 668 Ann Quinlan-Colwell, Sue Ballato, Greg Scott Firestone,
Case Scenario, 668 and Eva Pittman
Acknowledgments, 668 Organizational Commitment to Quality and Pain
References, 668 Management, 770
Contents xix
Organizational Initiatives to Support Quality of Safe Case Scenario, 792

and Effective Multimodal Pain Management, 772 References, 792
Quality Improvement, 781
Clinical Nursing Efforts to Support Organizational Appendix: Terminology, 797
Initiatives, 787
Education of Clinicians, 789 Index, 830
Future Opportunities for Improvement, 790
Key Points, 790
Assessment and Multimodal
Management of Pain
AN INTEGRATIVE APPROACH
2 Chapter 1 | The Evolution of Pain Assessment and Multimodal Analgesia as an Integrative Pain Management Approach
possible to obtain accurate data on the incidence and preva-

lence of pain. The challenges of collecting such data include
the subjective nature of pain, numerous definitions of pain,
methodologic issues, and infrequent research involving
epidemiologic studies of pain (Henschke, Kamper, &
Maher, 2015). This is complicated by different people not
only experiencing pain differently but also understanding
it and describing it differently. The same challenges exist
for collecting data regarding acute pain. However, this is
complicated by acute pain having a more elusive nature,
which results in most acute pain data being reported only
for postoperative and trauma pain (Rzewuska, Ferreira,
McLachlan, Machado, & Maher, 2015).
In a 2015 National Institutes of Health (NIH) report,
it was estimated that 126 million adults in the United
States experienced pain at some point during the previous
3 months, with 25.3 million (11.2%) reporting chronic
daily pain (Nahin, 2015). In addition, in 2015, chronic pain
was again described as causing clinical, social, and financial
challenges, with an estimated cost of more than $34 billion
annually in Australia and between $560 and $635 billion
annually in the United States (Henschke et al., 2015). These
Fig. 1.1 | Drawing by Louis La Forge based on Descartes’
description of Treatise of Man (1664). (Out of copyright.) figures do not include the loss of productivity incurred by
people living with pain (Dale & Stacey, 2016). The follow-
In this introductory chapter, an overview is presented, ing year, it was estimated that approximately half of people
including brief description of the evolution of pain being in Europe experienced at least one episode of pain, with a
understood as a complex multidimensional experience, 19% prevalence of chronic pain (Macfarlane, 2016).
the importance of assessing pain, and why an integrative The situation regarding acute pain is similar, with more
approach of managing pain with multimodal analgesia than 80% of people reporting pain after surgery and approx-
is the safest and most effective way to support people to imately 75% reporting moderate, severe, or extreme pain
best control pain. (Chou et al., 2016). Approximately half of all patients report
inadequately controlled postoperative pain (Polomano,
Dunwoody, Krenzischek, & Rathmell, 2008). Despite many
Incidence and Prevalence of Pain publications about acute pain after surgery, rigorous research
is needed to ascertain the prevalence and evidence to support
Pain is primarily a universal experience occurring among guidelines and recommendations for safe and effective multi-
humans and other animals. Even rodents with somato- modal management (Gordon, et al., 2016).
sensory cortex lesions who experienced asomaesthesia, or There is increasing awareness that unrelieved acute
the inability to recognize physical sensations, experienced pain results in chronic pain (Choinière, et al., 2014). This
pain at least through the inflammatory process even when is estimated to be as prevalent as 30% after some surgical
they were not able to process the sensations somatosenso- procedures (e.g., herniorrhaphy, thoracotomy, limb ampu-
rily (Uhelski, Davis, & Fuchs, 2012). The small number of tation, mastectomy) (Lovich-Sapola, Smith, & Brandt,
people who are diagnosed with a true painlessness disor- 2015). Additional research is needed to better understand
der either have a Mendelian genetic trait or an abnormal the extent to which acute pain is experienced and to more
development of pain receptor neurons (Nahorski, Chen, fully understand the evolution of acute pain to chronic
& Woods, 2015a; Nahorski, et al., 2015b). Although pain and how to prevent that from occurring after both
acute pain is a protective response to trauma or inflam- surgical and trauma pain situations (Bendayan, Ramírez-
mation, when unrelieved it is harmful and can evolve into Maestre, Ferrer, López, & Esteve, 2017; Chapman &
chronic pain (Chapman & Vierck, 2017). Vierck, 2017; Lovich-Sapola et al., 2015; Shipton, 2014).
In 1982, Khatami & Rush wrote: “Chronic pain is a
perplexing problem that costs billions of dollars annu-
ally in the United States alone. It affects family relations, Historical Perspective of Multimodal
job performance, emotional well-being, and even the Pain Management
doctor-patient relationship” (Khatami & Rush, 1982, p. 45).
Unfortunately, these words are surprisingly still accurate as The work of anesthesiologist John Bonica, who is considered
a description of chronic pain 35 years later. For many rea- the father of modern pain management, was instrumental
sons, despite the universality of the pain experience, it is not in the development and advancement of multidisciplinary
Chapter 1 | The Evolution of Pain Assessment and Multimodal Analgesia as an Integrative Pain Management Approach 3
pain management (Tompkins, Hobelmann, & Compton, extent, severity, and impact of pain on a worldwide level.
2017). Bonica, while working with injured soldiers in World Bonica’s work was instrumental in the formation of the
War II, recognized that despite the use of regional anesthetic American Pain Society (APS) and the IASP. His efforts
techniques, many of the soldiers did not have adequate pain encouraged a new focus on the study of pain, and over
relief and developed chronic pain (Tompkins et al., 2017). the years new pain theories were published, scientific
He reached out to colleagues in the fields of psychiatry, neu- inquiry into the field of pain expanded, and significant
rology, and orthopedics and noted that when his patients growth in the understanding of pain processes and path-
were seen by consultants from those specialties, pain and ways occurred. The identification of peripheral and cen-
functional outcomes improved. In the 1950’s based upon tral pain pathways led to great interest in pharmaceutical
his experiences, Bonica developed the first multidisciplinary research and the development of different classes of anal-
pain clinic, which was opened in Tacoma, Washington, gesic agents such as the nonsteroidal antiinflammatory
and relocated to the University of Washington in Seattle medications (Tompkins et al., 2017).
in the 1960s (Loeser, 2017). The treatment included mul-
tidisciplinary and integrative interventions such as physical
therapy, occupational therapy, and a variety of psychologic Early National Efforts to Address Pain
and cognitive approaches (Gatchel, McGeary, McGeary, & As scientific efforts to improve understanding and treat-
Lippe, 2014; Parris, & Johnson, 2014) (see Chapters 20, ment of pain evolved, there was growth in awareness of
21, 22). Pharmacologic approaches were also provided, but continued undertreatment of pain as a health care prob-
contrary to usual practice, scheduled medication adminis- lem. This awareness led to an initiative by the NIH to
tration, rather than as-needed (prn) dosing, was employed form a consensus development conference to address
(Tompkins et al., 2017). The patients in the multidisci- the issues and challenges associated with the need for
plinary clinic had significant improvements in outcomes, an integration of approaches to pain management (NIH,
including return to employment. Studies of patient out- 1986). Expert health professionals, including biomedical
comes in the multidisciplinary clinic compared to single researchers, physicians, dentists, psychologists, nurses,
discipline treatment, usual medical care, or no treatment, and others, along with representatives of the general
showed improved outcomes were an effect of the coordi- public, were brought together on May 19 to 21, 1986 to
nated biopsychosocial approach to care provided in the address the following questions (NIH, 1986):
multidisciplinary setting (Tompkins et al., 2017). As study
results were disseminated, multidisciplinary programs were • In what way should pain be assessed?
developed throughout the country and many of Bonica’s • In what ways should medications be used in an
integrative approaches to pain management were adopted integrated pain management approach?
(Tompkins et al., 2017). • How should nonpharmacologic approaches be used
Multidisciplinary pain clinics continued into the 1990s. in an integrated pain management approach?
Although this type of clinic still exists, the following fac- • What role does the nurse have in an integrated pain
tors contributed to the decline in the use of this approach management approach?
in the United States (Tompkins et al., 2017) • What are the future directions for pain management
research?
• Changes in insurance reimbursement practices from
bundled services to a fee-for-service model resulted in As an outcome of the conference, participants reached
financial losses in multidisciplinary clinics. consensus in response to these questions (NIH, 1986).
• The introduction of managed care changed payment It was agreed that pain is an important and complex
structures and carved out, or stopped, reimbursement phenomenon, and accurate pain assessment facilitates
for services such as physical therapy if the service was classification of pain and establishment of treatment
provided in the multidisciplinary clinic. objectives. It was also recognized that the management
• Academic medical centers, which often provided of pain is challenging, because although pain may be well
multidisciplinary pain clinics, closed the clinics because assessed, many variables and barriers, including personal
of financial losses associated with managed care. attitudes and lack of knowledge of health care providers,
• The growth of anesthesia-based pain fellowship may interfere with adequate treatment. The pivotal role
training programs increased the focus on procedure- of the nurse in the assessment and management of pain
based care rather than multidisciplinary care. was recognized. Agreement was reached that the nursing
role in pain management was expected to increase with
an integrated approach involving the multidisciplinary
health care team is necessary.
Growth in Pain Research The importance of both pharmacologic and nonphar-
Bonica was a major contributor to the development of macologic therapies in treating different types of pain was
pain research and progress in the field of pain manage- identified, and it became evident that no single modality is
ment in the latter half of the 20th century (Loeser, 2017). appropriate for the treatment of most people in pain. The
He published numerous studies that demonstrated the experts concluded the treatment of pain and the assessment
of response to treatment require an individualized approach In 1999 inadequate assessment of pain and pain
and appreciation for the multiple factors that have an impact relief was identified as the most significant factor con-
on each person’s pain experience and that future pain research tributing to the undertreatment of pain in U.S. hospitals
needed to explore these many factors. The consensus group (Max, Payne, Edwards, Sunshine, & Inturrisi, 1999).
recognized “an integrated approach to the assessment and Recognition of the importance of pain assessment led
management of pain brings greater options to individuals to the introduction of the phrase pain as the fifth vital
seeking the alleviation of pain” (NIH, 1986, para. 47). sign by the APS and adoption of this concept by the
As national awareness of the problem of poorly Veterans Health Administration in their national pain
managed pain continued to grow after the 1986 NIH strategy (Berry et al., 2001). Many embraced the use of
consensus conference, research efforts and interest in this phrase in efforts to ensure pain would be assessed on
the need for clinical improvements also increased. In a routine basis akin to vital signs (e.g., pulse, respiration,
1992 the Agency for Healthcare Policy and Research blood pressure). The introduction of standards for pain
(AHCPR; now the Agency for Health Care Research assessment and management by the Joint Commission on
and Quality [AHRQ]) published the first clinical prac- Accreditation of Healthcare Organization (JCAHO; now
tice guideline for pain management (Berry et al., 2001). the Joint Commission [TJC]) in 2000 furthered the adop-
This guideline addressed pain management in patients tion of practices to facilitate routine pain assessment.
undergoing operative or medical procedures and trauma. However, use of the phrase pain as the fifth vital sign was
Subsequently, in 1994 the AHCPR released a guideline eventually challenged and mostly abandoned, because
for the management of cancer pain. The developers of the critics opined that unlike vital signs that are objective,
1992 guideline, like those on the NIH consensus panel, pain is a subjective experience and complex phenomenon
acknowledged the undertreatment of pain, recognized the that may require assessment more or less frequently than
complexity and subjective nature of pain, and supported the need for vital sign measurement (Pasero, Quinlan-
the need for frequent accurate pain assessments, with the Colwell, Rae, Broglio, & Drew, 2016).
patient’s self-report (when possible) as the primary source Optimal pain management and appropriate multi-
of assessment. The 1992 guideline also emphasized the modal analgesia depend on appropriate assessment and
need for a collaborative, interdisciplinary approach to reassessment (Chou et al., 2016). The growth in the num-
pain, an individualized proactive pain treatment plan, the ber of unidimensional and multidimensional tools for the
use of pharmacologic and nonpharmacologic therapies to assessment of acute and chronic pain is the result of the
control pain, and the need for a formalized institutional cumulative efforts of the many individuals and organiza-
approach to acute pain management (AHCPR, 1992). tions that have advocated, over the years, to improve care
of patients with pain. Recent initiatives to improve pain
assessment practices include the development of tools
Pain Assessment as the Foundation that promote a social interaction, such as the multifaceted
of Multimodal Analgesia Clinically Aligned Pain Assessment (CAPA) tool, which
requires a conversation between clinician and patient to
One of the outcomes of the NIH consensus conference address five domains affected by pain (Topham & Drew,
was agreement about the importance of the assessment 2017). Many pain assessment tools have undergone
of pain. It was recognized that pain assessment needs to psychometric testing and are intended for use in differ-
include diagnostic evaluation and clarification of the goals ent patient populations, in patients with varied clinical
of care. Assessment should be specific to the type of pain, conditions, and in different clinical settings. Refer to
the cause of the pain, and the characteristics of the person Chapters 5, 6, and 7 for in-depth information related to
affected by pain. In the mid-1980s, most assessment tools pain assessment.
were based on the chronic pain model and were often A critical concept when assessing pain from an inte-
tools used in research, not clinical practice (NIH, 1986). grative perspective is that the pain experience involves
The McGill Pain Questionnaire, a multidimensional tool more than just an intensity rating; thus assessment of
developed by Melzack (1975), was introduced in 1975 pain must also involve additional components (Pasero
to measure the sensory-discriminative, motivational- et al., 2016). Emphasis is placed on the need to assess
affective, and cognitive-evaluative dimensions of pain in the impact of pain on an individual’s function. Although
the evaluation of pain therapies. Few valid and reliable function has been assessed as a component of some of the
tools were available for the assessment of acute pain. multidimensional tools used in chronic pain assessment, it
Unidimensional tools were mostly used in research to is only recently gaining attention as a dimension that may
measure pain intensity to determine effectiveness of phar- be incorporated in the acute pain assessment. Frequent
macologic and other pain interventions. For example, the reassessment of pain and function are critical to facilitate
visual analogue scale (VAS), introduced in 1964, and the optimal pain control, ensure patient safety, and gain the
numerical rating scale (NRS), introduced after the VAS, information needed to revise the analgesic plan of care
were initially used to compare effectiveness of analgesics for patients in the acute care setting (Chou, et al., 2016)
to placebo (Noble et al., 2005). and those being treated for chronic pain in primary care
settings (Anderson, Zlateva, Khatri, & Ciaburri, 2015). Rush included reports of significantly less pain, anxiety,
Several of the 2018 TJC pain standards include the need and depression with less analgesic use among the partic-
for consideration of function in establishing pain treat- ipants who completed their program (n = 14) compared
ment goals and assessing responses to multimodal pain with those who only partially completed their program.
relief measures (TJC, 2017). Nearly a decade later, Kehlet (1989) advocated to
As pain assessment practices and tools continue to proactively use combinations of analgesic medications
evolve, it is essential to recognize that an accurate pain as well as nonpharmacologic interventions to allevi-
assessment is fundamental to all efforts to alleviate pain. ate what he referred to as surgical stress. Subsequently,
Continued efforts to emphasize the importance of pain Kehlet and Dahl (1993) introduced the terms multimodal
assessment and develop practices and tools that support analgesia and balanced analgesia as a method for treat-
accurate pain assessment are necessary for the implemen- ing postoperative pain. The concept of using multimodal
tation of safe and effective integrative, multimodal pain analgesia in the management of postoperative pain con-
management approaches. tinued to slowly grow in use and acceptance during the
1990s (Doyle & Bowler, 1998; Michaloliakou, Chung,
& Sharma, 1996; Peduto, Ballabio, & Stefanini, 1998;
Evolution of an Integrative Sukhani & Frey, 1997).
Today, a multimodal treatment approach continues
Multimodal Approach for Pain to be the most effective way to help control chronic
Management (Multimodal Analgesia) pain (Dale & Stacey, 2016). Multimodal treatment was
recently defined by the IASP as being “the concurrent use
(Multimodal Treatment) of separate therapeutic interventions with different mech-
anisms of action within one discipline aimed at different
Early Support for Multimodal Analgesia pain mechanisms” (IASP, 2017). This definition is consis-
Although clinical care and treatment lagged behind the tent with the concepts of integrative health care and mul-
scientific understanding of pain, awareness of the value timodal analgesia. As information confirms the likelihood
of multimodal analgesia evolved slowly. Identification of acute pain progressing to chronic pain, a multimodal
of opioid receptors in the brain and spinal cord in the approach for acute pain is also advocated (Chou et al.,
1970s led to research that demonstrated the benefits of 2016; Lovich-Sapola et al., 2015) (Fig. 1.2).
adding opioids to local anesthetic epidural solutions a It is important to distinguish polypharmacy from mul-
decade later (Kehlet & Dahl, 1993). During the 1980s, timodal analgesia. Polypharmacy occurs when multiple
experts researched the phenomenon of poorly con- medications are prescribed when they are not necessary
trolled acute postoperative pain and began to employ and/or are not indicated (Maher, Hanlon, & Hajjar,
treatment approaches that included combinations of 2014). Multimodal analgesia is the intentional use of two
systemic NSAIDs with opioids. The use of opioids and or more medications (and/or nonpharmacologic inter-
local anesthetics in epidural solutions expanded, and ventions) with various mechanisms of action that act in
the addition of the alpha-2 agonist clonidine to epi- different locations on the pain pathway (Buvanendran &
dural solutions was introduced (Kehlet, 1989; Kehlet Kroin, 2009). Therefore appropriate assessment of pain
& Dahl, 1993). Likewise, in the 1980s, interest began is critical in determining the particular multimodal anal-
to develop in the use of nonopioid analgesics and tri- gesia components appropriate to safely and effectively
cyclic antidepressants along with opioids to improve control for each patient.
pain relief for patients with cancer (Richlin, Jamron, &
Novick, 1987).
One of the first uses of the term multimodal analgesia The Increase in Opioid Prescribing
in the pain-related literature was by Khatami and Rush On an international level, the World Health Organization
in their February 1982 article describing the multimodal (WHO), recognizing the prevalence and incidence of
treatment program used in a pilot study with five people cancer pain in developed and developing countries, pro-
living with chronic pain and in the 1-year follow-up of claimed the treatment of pain as a universal right, and
a subsequent study (n = 23) using the same psychology- developed cancer pain treatment guidelines. These guide-
based multimodal approach (Khatami & Rush, 1978; lines, referred to as the WHO Analgesic Ladder, consist
Khatami & Rush, 1982). Their studies were based on the of a three-step approach ranging from the use of nonopi-
hypotheses that there are both interpersonal and intra- oids, to weak opioids, and to strong opioids depending on
personal determinants involved with chronic pain and the patient’s pain level and response to treatment (WHO,
chronic pain could be better controlled by addressing 1986). The WHO Analgesic Ladder supports the use of a
symptoms, stimuli, and social system alterations. Their multimodal approach to cancer pain management, with
hypothesis was consistent with the earlier multidimen- recommendation for the use of nonopioid analgesics and
sional model developed by Melzack and Casey (1968). adjuvant agents at every step in the ladder (Ventafridda,
The results of the 1-year follow-up study by Khatami and Tamburini, Caraceni, & Naldi, 1987).
Fig. 1.2 | The sites of action of broad-analgesics. Targeting multiple distinct components in the pain-signaling pathway—transduction, transmission,
perception, and modulation—is increasingly viewed as offering additive, perhaps even supra-additive (synergistic) pain reduction. Coadministration
of the α2-receptor agonist clonidine along with an opioid, for example, may yield significantly greater analgesic effects when compared with either
agent alone. Although the neural pathways that govern pain are yet to be fully elucidated, a balanced analgesic approach using multiple agents with
unique modes of action is thought to reduce the peripheral and central sensitization and inflammation that often characterize chronic pain disorders.
Adapted from D.J. Kelly, M. Ahmad, S.J. Brull, Preemptive analgesia I: physiological pathways and pharmacological modalities, Can J Anaesth, 48
(2001). In Gudin J. Opioid therapies and cytochrome interactions. J Pain Symptom Manage 2012; 44(6 Suppl), S4-S14
During the 1980s the use of opioids to treat cancer pain, measures included a call for the therapeutic use of opioids
particularly near the end of life, expanded in the United along with reassurance about the low risks for addiction
States as a result of advocacy by palliative care experts. (Baker, 2017). Limited available data demonstrated a low
Awareness of the WHO Analgesic Ladder increased, incidence of addiction in patients on opioid therapy for
and guidelines were slowly adopted in clinical practice. noncancer pain, but well-designed studies were lacking.
Initiatives in the 1990s led to the expansion of multimodal Russell Portenoy, an expert palliative care physician,
approaches beyond the treatment of cancer pain to chronic wrote “controlled clinical trials of long-term opioid ther-
noncancer pain. Experts called for the use of pharmaco- apy are needed, but the lack of these trials should not
logic and nonpharmacologic approaches, but controversy exclude empirical treatment (with opioids) when medi-
existed about the use of opioids to treat chronic noncancer cal judgment supports it and therapy is undertaken with
pain (Portenoy, 1996). Until then, opioids were rarely used appropriate monitoring” (Portenoy, 1996, p. 212).
for chronic noncancer pain because of concerns about the When concern about opioid use in patients with non-
risks of tolerance, addiction, side effects, and impact on cancer pain was raised, the 1980 Porter and Jick study was
function. Clinical experience demonstrated that the ben- often cited as attesting to the safety of using opioids and the
efits of long-term opioid use in the treatment of cancer low risk for developing a substance use disorder (Compton
pain markedly outweighed the presumed risks. Based on & Volkow, 2006; Iles, Catterall, & Hanks, 2002; Kowal,
this experience and with heightened awareness of the 1998; Porter & Jick, 1980; Portenoy & Foley, 1986; Rich,
inadequate treatment of chronic noncancer pain, experts 2001). This reference was cited more than 600 times
in the pain community began to debate and consider the between 1980 and 2017 (Leung, Macdonald, Stanbrook,
use of opioids in this population (Large & Schug, 1995; Dhalla, & Juurlink, 2017). In actuality the frequently
Portenoy, 1996; Turk, Brody, & Okifuji, 1994). cited study, which reported that only 4 patients among
In 1990 the president of the APS brought attention to nearly 12,000 developed addiction after being treated
the problems of inadequate pain assessment and treatment with opioids, was reported in a letter of five sentences to
and outlined necessary improvement measures. These the editor, with no supporting documentation, (Porter &
Jick, 1980). All of the patients whose medical records Tabler, 2017). With heightened awareness of the risks for
were reviewed received opioids for a ‑limited period in an opioid-related complications, opioids continue to have a
acute care setting. Years later, Dr. Jick shared that he never role in pain management when used cautiously and with
intended for the information to be generalized (Hawkins, monitoring for effectiveness and unintended effects.
2017). This experience is important and serves to remind
clinicians of their responsibility to critically evaluate
reported data and assess whether it is appropriate to gen- Resurgence of Support for Integrative,
eralize the information to different populations. Multimodal, Opioid-Sparing Approaches
Opioid use increased significantly in the 1990s and An increased interest in multimodal, opioid-sparing
early 2000s. The rise in use has been attributed to many approaches has emerged in recent years. Using the various
factors including pain management expert support, an pharmacologic and nonpharmacologic interventions in a
increased focus on the importance of pain management coordinated integrative approach facilitates pain control
by health care providers and the general public, addition that is patient specific and evidence based, incorporat-
of pain management standards by TJC in 2000, efforts ing complementary therapies (e.g., relaxation, cognitive
to optimize patient satisfaction with pain control on behavioral therapy, energy work) in conjunction with tra-
Hospital Consumer Assessment of Healthcare Providers ditional allopathic health care options (e.g., medications,
and Systems (HCAHPS) surveys, and increased availabil- interventions) through therapeutic relationships to facil-
ity and marketing of new opioid preparations such as itate healing of the entire person (Ring & Mahadevan,
extended-release oxycodone (Tompkins et al., 2017). 2017; Sundberg et al., 2014; Twillman, 2017). This
approach can be traced to Aristotle, who thought each
person is a seamless composite of mind, body, and spirit;
Rise in Opioid-Related Complications however, that perspective was eclipsed by the Cartesian
As opioid use increased, complications of opioid use also split of body (medicine) and mind-spirit (church) (Rakel
increased in health care and community settings. The use & Weil, 2018). Integrative health care allows for pain to
of opioids to treat acute pain has been associated with be addressed from physical, cognitive, emotional, spiri-
serious opioid-related adverse events, including respira- tual, and psychologic perspectives appropriate for the
tory depression and death (Gupta et al., 2018; Lee et al., individual person experiencing the pain in the manner in
2015; Weingarten, Warner, & Sprung, 2017). A number which it is being experienced in collaboration with clini-
of agencies, including the TJC and the Institute for Safe cians who work with patients from an evidence-informed
Medication Practices (ISMP), issued warnings about the position (Rosenthal & Lisi, 2014) (Table 1.1). From this
increase in serious complications of prescription opioid viewpoint, pain management is planned through shared,
use, including oversedation, respiratory depression, sei- evidence-based decision making with the patient to opti-
zures, and death (TJC, 2012; Institute for Safe Medication mize wellness and function consistent with the goals and
Practices, 2007). In a sentinel event alert, TJC addressed values of the individual patient (Twillman, 2017).
the safe use of opioids in the hospital setting and rec- An integrated, multimodal approach for pain man-
ommended the use of “an individualized multimodal agement is used with increased frequency to control pain
treatment plan . . . (that) combines strategies such as psy- with various causes in a diversity of settings. In the post-
chosocial support, coordination of care, the promotion operative arena, multimodal analgesia is often used as
of healthful behaviors, nonpharmacologic approaches, a preventive intervention to minimize or prevent acute
and nonopioid pain medications” (TJC, 2012). postoperative pain and the development of chronic pain
The rise in opioid availability also has been associated (Rosero & Joshi, 2014). The authors of an extensive sys-
with a marked increase in problems of opioid abuse and tematic review that included patients undergoing abdom-
diversion. The marked increase in opioid-related com- inal, orthopedic, gynecologic, cosmetic, spinal, urologic,
plications, including the rise in opioid use disorders and cardiothoracic, and gastric bypass surgeries, discussed
opioid-related deaths, has led to the recognition that the the various modes of analgesia regarding the particu-
national opioid crisis in the United States is a real public lar surgeries (Gritsenko, Khelemsky, Kaye, Vadivelu, &
health concern, with almost 20,000 deaths reported during Urman, 2014). The authors of another systematic review
2014 (White, 2017). Many local, state, and national efforts reported that topical nonsteroidal antiinflammatory
have been developed to address the individual and societal drugs (NSAIDs) may be effective as a part of multimodal
problems associated with inappropriate use of prescribed analgesia after a variety of abdominal, gynecologic, and
and nonprescribed opioids and the problems associated skin grafting surgeries (Brubaker, Kendall, & Reina,
with opioid use disorders. In response to this crisis, numer- 2016). An integrated multimodal approach is effective
ous states and institutions have placed limitations on the for sparing opioids in managing pain among trauma
quantities of opioids that can be prescribed (Martin, patients (Sullivan, Lyons, Montgomery, & Quinlan-
Laderman, Hyatt, & Krueger, 2016). Clinicians are now Colwell, 2016). In France a multimodal approach is
finding themselves being held legally responsible for nega- strongly recommended in the guidelines for caring for
tive effects of opioids, including opioid abuse (Savarese & patients with chest trauma (Bouzat et al., 2017).
Table 1.1 | Themes of Integrative Health Care Applied to Multimodal Analgesia

Integrative Health Care Theme Application to Multimodal Analgesia
Combined use of complementary and conventional Traditional allopathic health care is used in conjunction with complementary
(allopathic, traditional Western) health care with nonpharmacologic interventions by clinicians with specialized preparation to best
representatives of a variety of health care disciplines control pain through a multimodal approach to optimize safe pain management.
contribute to providing care of the patient.
Integrative health care is patient centered. Not only is the focus of care on the patient but the patient is actively involved in
planning and implementing pain management interventions that are specific to
the individual needs, values, lifestyle, and preferences.
An integrative approach considers the person as a Pain is understood to be a multifaceted experience involving all aspects of the
whole being including body, mind, emotions, and person, including body, mind, emotion, and spirit. Effective management must
spirit. consider all of these aspects and provide a variety of interventions appropriate for
the individual person.
Interprofessional collaboration is a key component of Clinicians from various conventional health care disciplines (e.g., anesthesia,
integrative health care. neurology, nursing, psychology, physical therapy, etc.) coordinate with clinicians
from complementary modalities (e.g., energy modalities, movement therapy,
music therapy, herbalists, pet therapy, etc.) coordinate their activities to optimize
helping the person to best control pain in a safe manner.
Integrative care is evidence based or evidence Approaches, interventions, and treatments used are based on evidence, and the
informed (using information from research and the evidence informs and guides a multimodal analgesic approach to managing pain.
interpretation of data to guide practicea).
Health determinants and environment are important An integrative approach to pain management considers the particular
considerations in integrative health care. environment and lifestyle of the person with pain and any barriers that limit which
interventions can be used.
Focus is on optimal health and wellness. Rather than focusing on cure, integrative health care focuses on optimizing health
and wellness. The goal is to support the person to be as well as possible while
controlling pain with a variety of interventions in a safe and effective manner to
function at the highest level possible.
Relationship between the various health care Effective pain management is based on a compassionate therapeutic relationship
providers with the patient is important. in which respect and informed decision making support the person with pain to
best control pain and function at the highest level possible.
a
Data from Brown, C., & Rogers, S. (2014). Measuring the effectiveness of knowledge creation as a means of facilitating evidence-informed practice in early years settings in one
London borough. London Review of Education, 12(3), 245–260.
Based on Rosenthal, B., & Lisi, A. J. (2014). A qualitative analysis of various definitions of integrative medicine and health. Topics in Integrative Health Care, 5(4). ID 5.4004.
medication and techniques that target different mecha-

Drivers for Integrative, Multimodal, nisms of action with the peripheral and/or central nervous
system (which might also be combined with nonpharma-
Opioid-Sparing Approaches cologic interventions) might have additive or synergis-
tic effects and more effective pain relief compared with
Professional Organizations
single-modality interventions” (Chou et al., 2016, p. 136).
Through position statements and clinical practice guide- The committee clarified that the particular components
lines, a number of professional organizations have issued of a multimodal regimen need to be individualized for
recommendations for the use of multimodal analge- the patient considering the surgical procedure and setting
sia. In 2016 the APS, the American Society of Regional (Tables 1.2 and 1.3).
Anesthesia and Pain Medicine, and the American Society In 2009 the American Society for Pain Management
of Anesthesiologists collaborated to develop guidelines Nursing (ASPMN, 2009) issued a call to revolutionize
for postoperative pain management (Chou et al., 2016). pain care in the United States, noting an organizational
The committee strongly recommended multimodal reg- belief that a multimodal and balanced approach to
imens of analgesia, which they found is supported by managing pain is crucial to rectify the undertreatment of
high-quality evidence. In those guidelines, multimodal pain. This was followed in 2015 with a commitment to
analgesia is defined as “the use of a variety of analgesic further advance pain management among patients with
chronic pain through multimodal approaches (ASPMN, The Joint Commission

2015). In position statements addressing pain in various
situations, ASPMN endorsed maximizing multimodal With increasing awareness of the national crisis associ-
analgesia, including nonpharmacologic interventions, ated with opioid use disorder, various groups and orga-
nonopioid analgesics, and opioids (Czarnecki et al., nizations have been singled out as having contributed to
2011; Jarzyna et al., 2011; Oliver et al., 2012; Pasero the crisis.
et al., 2016). TJC’s emphasis on pain management and development
The IASP, an organization formed under the leadership of pain standards has been cited as a contributing factor
of John Bonica, has had a long history of supporting mul- to the widespread opioid problem. In response to this crit-
tidisciplinary approaches to pain management. In carry- icism, in 2011, the following was added to the standards:
ing out its mission to “bring together scientists, clinicians, Both pharmacologic and nonpharmacologic strategies
health-care providers, and policymakers to stimulate and have a role in the management of pain. The following
support the study of pain and to translate that knowledge examples are not exhaustive, but strategies may include the
into improved pain relief worldwide” (IASP, 2018), the following: Nonpharmacologic strategies: physical modali-
IASP has provided many resources and supported numer- ties (for example, acupuncture therapy, chiropractic ther-
ous initiatives to educate health professionals about pain apy, osteopathic manipulative treatment, massage therapy,
mechanisms and the management of pain. One of the and physical therapy), relaxation therapy, and cognitive
IASP’s educational initiatives includes the publication behavioral therapy; Pharmacologic strategies: nonopioid,
of the IASP Taxonomy, which aids health providers in opioid, and adjuvant analgesics. (Baker, 2017, p. 6)
sharing a common language and understanding of terms The 2018 TJC pain standards have undergone signifi-
related to pain. As mentioned earlier, as a result of the cant revisions that have resulted in an increased emphasis
work of the IASP Multimodal Pain Therapy task force, on the need for safety in opioid prescribing, patient edu-
the term multimodal treatment was clarified and defined cation, and multimodal pharmacologic and nonpharma-
in 2017. cologic approaches to pain (Baker, 2017).
Centers for Disease Control and Prevention Enhanced Recovery After Surgery Society
Guidelines Guidelines
In 2016 the Centers for Disease Control and Prevention The growing adoption of the Enhanced Recovery After
(CDC) published “A Guideline for Prescribing Opioids Surgery (ERAS) Society guidelines is a significant driver
for Chronic Pain.” The guideline was developed to assist for the use of multimodal analgesia. ERAS guidelines
primary care providers to prescribe opioids appropri- provide a multimodal, evidence-based approach to pre-
ately in the treatment of chronic noncancer pain (Dowell, operative, intraoperative, and postoperative care for the
Haegerich, & Chou, 2016). The goal of this initiative was purpose of improving surgical outcomes (Beverly, Kaye,
to reduce opioid-related risks, including opioid use disor- Ljungqvist, & Urman, 2017). Early ERAS guidelines were
der, overdose, and death (Dowell et al., 2016). The CDC applied to the care of patients undergoing colorectal sur-
publication has resulted in some controversy because gery. Since then, guidelines have been developed for the
questions have been raised related to the lack of transpar- care of patients undergoing a variety of major surgical
ency in guideline development, potential bias against opi- procedures (Beverly et al., 2017). Surgical pathways that
oids on the part of some guideline authors, and concerns adopt the ERAS guidelines address the need for well-
about barriers to appropriate opioid access (Schatman & controlled postoperative pain because it is recognized that
Ziegler, 2017). Despite the controversy, the guideline sup- inadequate postoperative pain control and excessive opi-
ports the use of multimodal approaches and endorses non- oid use may interfere with the goals of ERAS initiatives
pharmacologic interventions and nonopioid analgesics as and delay return of bowel function, oral intake, mobili-
the preferred treatments for chronic pain (Dowell et al., zation, and discharge and may increase readmission rates
2016). When opioids are necessary, the CDC recommends (Tan, Law, & Gan, 2015). The guidelines include the
the concomitant use of nonpharmacologic and nonopioid use of multimodal, opioid-sparing approaches to reduce
analgesic measures. Thus the CDC guidelines reaffirm the opioid-related side effects. These approaches are initiated
support for multimodal analgesia that was introduced by preoperatively, often with the use of acetaminophen, cele-
Khatami and Rush over three decades earlier. Subsequent coxib, and gabapentin, are employed intraoperatively with
to publication of the guidelines, CDC representatives dis- the use of regional anesthetic and analgesic techniques and
cussed the importance of understanding the population opioid-sparing anesthetics and continued postoperatively
addressed with those guidelines, the need for develop- with continued use of scheduled nonopioids, regional
ment of nonopioid analgesia, the importance of basing techniques, and opioids on an as-needed basis. In many
decisions on supporting evidence, and respecting the need hospitals, multimodal analgesia is a standard component
for some patients to continue with higher dose opioids in ERAS plans of care (Montgomery & McNamara,
(Dowell, Haegerich, & Chou, 2019). 2016).
Institute of Medicine Report Future Challenges and Opportunities

In 2010 the Institute of Medicine (IOM; now the National for Multimodal Analgesia Within an
Academy of Medicine), in response to a directive from the
U.S. Department of Health and Human Services (DHHS) Integrative Approach
issued through the NIH, “conducted a study to assess
the state of the science regarding pain research, care, and Perhaps at no time has the evolution of knowledge,
education and to make recommendations to advance perspective, and interventions regarding pain been so
the field” (National Research Council, 2011, p. 20). The rapid and so diverse as it has been during the last two
report, issued a year later, identified pain as a public health decades, particularly since the beginning of the 21st
problem and summarized many of the challenges in the century. However, challenges to effective pain manage-
assessment and treatment of chronic pain. Throughout ment continue. These include (1) to use the knowledge
the report, multiple statements addressed the importance gained to most effectively help patients who are suffer-
of multidisciplinary and multimodal approaches to pain ing each day with pain, (2) to minimize the occurrence
assessment and treatment. of unrelieved pain, (3) to continue to gain information
to better understand pain processes, (4) to educate cli-
nicians about new advances within the realm of an inte-
National Pain Strategy
grative multimodal approach for better managing pain
After the publication of the IOM report, the DHHS in patient-focused partnerships, and (5) to continue to
requested the Interagency Pain Research Coordinating search for the safest and most effective interventions for
Committee (IPRCC) to coordinate efforts to address pain management.
the recommendations in the IOM report and develop Sadly, many of the multimodal options are not avail-
the National Pain Strategy (NPS). Experts from private able for many people. Some areas may not have provid-
and public organizations worked collaboratively to for- ers who are knowledgeable in multimodal analgesia. In
mulate the NPS, which was published in 2015. Among other areas there is a scarcity of multimodal treatment
the many statements in the NPS that support the use of providers, particularly those who provide nonpharma-
multimodal analgesia is one that states, “effective pain cologic interventions. Nonopioid components of multi-
care must emphasize shared decision making, informed modal treatment may be cost prohibitive to people who
pain assessment, and integrated, multimodal, and are underinsured or uninsured (Dale & Stacey, 2016)
interdisciplinary treatment approaches that balance (see Chapter 4). Technology offers an opportunity to
effectiveness with safety” (IPRCC, 2015, p. 16). The incorporate nonpharmacologic interventions in a cost-
impact of this initiative has yet to be realized because effective and easily accessible manner for people living
the national opioid crisis has overshadowed efforts with chronic pain to use to self-manage pain as part of
focused on pain relief. an integrative multimodal approach (Heapy et al., 2015).
Passage of the Comprehensive Addiction and Recovery An important factor for the future is increasing support
Act of 2016 (CARA) resulted in the DHSS formation of for rigorous research with good methodology. Research is
the Pain Management Best Practices Inter-Agency Task needed to investigate the multimodal analgesic benefit of
Force (Task Force) to address acute and chronic pain existing medication combinations (Dahl et al., 2014), and
in the context of the opioid crisis (U.S. Department of the investigation of new analgesic medications and their
Health and Human Services, 2019). The Task Force role within a multimodal plan of care is welcomed. The
included representatives from the U.S. Department of benefits of the various nonpharmacologic interventions for
Defense and the U.S. Department of Veterans Affairs managing pain and their role in a multimodal analgesic
with the Office of National Drug Control Policy, as well plan of care is needed. One of the most important areas
as non-federal representatives from the general public of future research is to further explore ways in which an
and professionals from diverse disciplines and views, integrative approach with multimodal analgesia can be
including experts in areas related to pain management, used to effectively manage postoperative pain (Rosero
pain advocacy, addiction, recovery, substance use disor- & Joshi, 2014; Vadivelu et al., 2014) and minimize the
ders, mental health, minority health, and more. The Task development of chronic pain (Clarke et al., 2015). Using
Force finalized a report in 2019 that stressed the impor- multimodal analgesia in a preventive manner to prevent
tance of individualized patient-centered care, based chronic pain in infants and children is an area in which
on a biopsychosocial care model, in the diagnosis and there is scant research, and is much needed (Friedrichsdorf,
treatment of acute and chronic pain. This detailed report 2016). Additional research is needed to explore the use of
emphasizes the importance of pain and risk assessment technology and the effectiveness of technologic applications
and strongly supports the use of multidisciplinary and as components of integrative multimodal analgesic plans
multimodal approaches to acute and chronic pain, of care (Heapy et al., 2015). Finally, perhaps there needs to
including use of medications, interventional approaches, be a reevaluation of the concepts of evidence-based prac-
and physical therapies (U.S. Department of Health and tice and the goals of research in pain management, keeping
Human Services, 2019). a focus on safety (Robinson, 2016) and quality of life.
Table 1.2 | Options for Components of Multimodal Therapy for Commonly Performed Surgeries
Local,
Systemic Intraarticular
Type of Pharmacologic or Topical Regional Anesthetic Neuraxial Anesthetic Nonpharmacologic
Surgery Therapy Techniquesa Techniquesa Techniquesa Therapiesb
Thoracotomy Opioidsc Paravertebral block Epidural with local anesthetic Cognitive modalities
(with or without opioid), or TENS
intrathecal opioid
NSAIDsd and/or
acetaminophen
Gabapentin or
pregabalind
IV ketaminee
Open Opioidsb Local anesthetic at Transversus abdominis Epidural with local anesthetic Cognitive modalities
laparotomy incision plane block (with or without opioid), or TENS
intrathecal opioid
NSAIDsd and/or IV lidocaine infusion

acetaminophen
Gabapentin or
pregabalind
IV ketaminee
IV lidocaine
Total hip Opioidsc Intraarticular local Site-specific regional Epidural with local anesthetic Cognitive modalities
replacement anesthetic and/or anesthetic technique (with or without opioid), or TENS
opioid with local anesthetic intrathecal opioid
NSAIDsd and/or
acetaminophen
Gabapentin or
pregabalind
IV ketaminee
Total knee Opioidsc Intraarticular local Site-specific regional Epidural with local anesthetic Cognitive modalities
replacement anesthetic and/or anesthetic technique (with or without opioid), or TENS
opioid with local anesthetic intrathecal opioid
NSAIDsd and/or
acetaminophen
Gabapentin or
pregabalind
IV ketaminee
Spinal fusion Opioidsc Local anesthetic at Epidural with local anesthetic Cognitive modalities
incision (with or without opioid), or TENS
intrathecal opioid
Acetaminophenb
Gabapentin or
pregabalind
IV ketaminee
Continued
Table 1.2 | Options for Components of Multimodal Therapy for Commonly Performed Surgeries—Cont’d
Local,
Systemic Intraarticular
Type of Pharmacologic or Topical Regional Anesthetic Neuraxial Anesthetic Nonpharmacologic
Surgery Therapy Techniquesa Techniquesa Techniquesa Therapiesb
Cesarean Opioidsc Local anesthetic at Transversus abdominal Epidural with local anesthetic Cognitive modalities
section incision plane block (with or without opioid), or TENS
intrathecal opioid
NSAIDsd and/or
acetaminophen
CABG Opioidsc Cognitive modalities

TENS
Acetaminophen
Gabapentin or
pregabalind
IV ketaminee
a
Intraarticular, peripheral regional, and neuraxial techniques typically not used together.
b
Use as adjunctive treatments.
c
Use IV PCA when parenteral route needed for more than a few hours and patients have adequate cognitive function to understand the device and safety limitations.
d
May be administered preoperatively.
e
On the basis of panel consensus, primarily consider for use in opioid-tolerant or otherwise complex patients.
Note: Blank cells indicate techniques generally not used for the procedure in question.
CABG, Coronary artery bypass grafting; IV, intravenous; NSAIDs, nonsteroidal antiinflammatory drugs; PCA, patient-controlled analgesia; TENS, transcutaneous electrical nerve
stimulation.
Chou, R., Gordon, D. B., de Leon-Casasola, O. A., Rosenberg, J. M., Bickler, S., Brennan, T., . . . & Griffith, S. (2016). Management of postoperative pain: A clinical practice guideline
from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional
Anesthesia, Executive Committee, and Administrative Council. The Journal of Pain, 17(2), 131–157.
Table 1.3 | Summary of Interventions for Management of Postoperative Pain
Intervention Suggested Use Comments Contraindications and Cautions

Nonpharmacologic Might require preoperative education
therapies and patient training for optimal results
Transcutaneous Consider as an adjunct to other Typically applied at incision site Pacemaker or implanted
electrical nerve postoperative pain management defibrillator, lymphedema, broken
stimulation treatments skin
Cognitive Consider as an adjunct to other Includes guided imagery and other None, caution in patients with
modalities postoperative pain management relaxation methods, hypnosis, history of psychosis
treatments intraoperative suggestions, and music
Systemic
pharmacologic
therapies
Acetaminophen Use as component of Reduces use of postoperative opioids Acetaminophen: hepatotoxicity

and NSAIDs multimodal analgesia No clear difference between IV and oral NSAIDs: gastrointestinal bleeding
administration and ulceration, cardiovascular
events, renal dysfunction
NSAIDs contraindicated in patients
who undergo coronary artery
bypass surgery
Table 1.3 | Summary of Interventions for Management of Postoperative Pain—cont’d

Celecoxib usually dosed at 200–400 mg
30 min to 1 h preoperatively and then
200 mg bid postoperatively
Acetaminophen usually dosed at

500–1000 mg PO or IV q6h
Some observational evidence of

association between high-dose NSAIDs
and nonunion in spinal fusion and
surgery for fractures, and between
NSAID use and anastomotic leak in
intestinal surgery
Oral opioids Use as component of Oral is the preferred route for patients Respiratory depression, potential
multimodal analgesia who can take oral medications for addiction and abuse, sedation,
nausea and vomiting, constipation
Patient controlled Use when the parenteral route Avoid basal infusion of opioids in opioid- See Oral opioids
IV analgesia with is needed for postoperative naive adults
opioids systemic analgesia for more
than a few hours
Gabapentin and Consider as a component Gabapentin doses vary; in trials Dizziness, sedation; reduced dose
pregabalin of multimodal analgesia, usually dosed at 600–1200 mg 1–2 h with renal dysfunction
primarily studied in patients preoperatively, 600 mg postoperatively
who underwent major surgery, (single or multiple doses)
opioid-sparing
Pregabalin doses vary; in trials usually

dosed at 100 or 300 mg preoperatively or
150 or 300 mg preoperatively followed by
the same dose 12 h later
Higher doses might be more effective,

but also might be associated with
increased sedation
Ketamine IV Consider as a component Dosing varies widely, consider Patients with history of psychosis
of multimodal analgesia, in preoperative bolus of 0.5 mg/kg followed Hallucinations, nightmares,
patients who undergo major by an infusion at 10 mcg/kg per min dissociative symptoms
surgery, opioid-sparing intraoperatively, with or without a
postoperative infusion at a lower dose
Limited evidence for use in children
Lidocaine IV Consider as a component Dosing varies, consider induction dose Conduction block
of multimodal analgesia in of 1.5 mg/kg followed by 2 mg/kg per h Dizziness, seizures, bradycardia
patients who undergo open and intraoperatively
laparoscopic abdominal surgery
Local,
intraarticular, and
topical therapies
Continued
Table 1.3 | Summary of Interventions for Management of Postoperative Pain—cont’d

Local anesthetic Use local anesthetic infiltration Clinicians should be knowledgeable See Lidocaine IV; also local pain,
infiltration at incision site for surgical regarding specific local anesthetic infection, bleeding
procedures for which there infiltration techniques
is evidence showing benefit
(examples: cesarean section,
laparotomy, and hemorrhoid
surgery)
Intraarticular local Use intraarticular injections Clinicians should be knowledgeable See Lidocaine IV and Oral opioids;
anesthetic and/or for surgical procedures for regarding specific intraarticular injection also local pain, infection, bleeding;
opioid which there is evidence of techniques. potential chondrolysis with
benefit (examples: hip, knee, and intraarticular shoulder injections
shoulder surgery)
Caution with use of continuous

intraarticular bupivacaine in shoulder
surgery because of association with
chondrolysis
Topical local No recommendations for use in 4% Liposomal lidocaine or eutectic See Lidocaine IV; also local pain,
anesthetics adult postoperative pain. Use mixture of local anesthetics, lidocaine infection, bleeding, rash
suggested in combination with and procaine
penile nerve block in infants
undergoing circumcision.
Peripheral regional
and neuraxial
analgesic therapies
Peripheral regional Use as part of multimodal Clinicians should be familiar with See Lidocaine; also potential for
anesthetic analgesia for surgical specific regional anesthetic techniques falls
techniques procedures for which there is
evidence of benefit (examples:
thoracotomy, lower or upper
extremity surgery, hemorrhoid
surgery, circumcision)
Use continuous over single injection

techniques when longer duration of
analgesia is required
Neuraxial analgesia Use for major thoracic, No clear difference between continuous See Lidocaine and Oral opioids; also
(epidural with local abdominal, cesarean section, infusion with epidural catheter versus motor weakness and risk of falls
anesthetic [with or and lower extremity surgery single dose of intrathecal morphine
without opioids] or
intrathecal opioid)
bid, Twice per day; IV, intravenous; NSAIDs, nonsteroidal inflammatory drugs; PO, orally.
Note: Table data are not listed in order of preference or strength of evidence. The choice of treatments must be made on the basis of comprehensive patient assessment and
the available evidence with consideration of multiple factors, including individual risk factors for adverse events, comorbidities, cost, patient response; combinations of
medications and techniques are often indicated. Doses are for typical adults.
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line from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists’ Committee on Regional
Anesthesia, Executive Committee, and Administrative Council. The Journal of Pain, 17(2), 131–157.
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Herodotus does not tell the tale of its
THE FATE OF
CARIA?
reduction. All that he says is that, “after the fall
of Miletus [in 494], the Persians immediately
H. vi. 25. got possession of Caria, some of the cities
surrendering voluntarily, others being brought to
submission by force.”
But the absence of any record of Carian participation in the revolt
during the long period intervening between the Persian defeat near
Pedasos and the fall of Miletus, suggests the suspicion that these
“voluntary surrenders” are not in all cases attributable to the time
following the fall of that city.
H. vi. 20.
The people of that very town Pedasos are, in the
settlement of affairs made after the capture of Miletus,
granted by the Persians a portion of the late Milesian territory. It
would seem as if Caria, partially, at any rate, made terms with her
old masters; as if Artaphernes made a successful trial of diplomacy
in the critical time which succeeded the great defeat, and detached
Caria from the cause of the insurgents by offering her a share in the
spoils of her allies. This hypothesis explains, at any rate, two
features in the history of this time which would otherwise be
inexplicable, namely, the apparent non-participation of Caria in the
years following the Persian defeat, and the unexpected grant made
by the Persians to a Carian city.
Whatever may be the truth with regard to Caria, it is plain that she
was a negligible quantity at the time when the great attack on Miletus
was planned.
The attack was to be of a twofold character, by sea as well as
land. The naval forces of Persia had already suffered two severe
defeats in the course of the war. On these two occasions the
Phœnicians had proved inferior to the Ionians on the sea. But the
H. vi. 6.
fleet in the present instance was drawn not merely
from Phœnicia, but also from Cilicia and Egypt, and
even from that Cyprus which, but two short years before, had fought
as an ally of the Ionians. Both sides regarded this great effort as the
crisis of the struggle.
Delegates from the Ionian towns met at the pan-Ionian sanctuary
of Poseidon near Mykale, to concert measures to meet the great
attack. Their decision was a somewhat remarkable one. They
determined to confine the operations on land to the defence of the
actual walls of Miletus, which should be conducted by the Milesians
themselves; but to mobilize the whole of their available navy and to
station it at Ladé, a small island off the town of Miletus.
It was a great misfortune to the Ionian cause at this time that the
war operations of the League were not directed by one man of
ability. There may have been able men in the pan-Ionian Council; but
in war such a Council is apt to err on the side of caution, and to
adopt a purely defensive attitude, when the offensive would be the
best defence. The main features of the situation are sufficiently clear.
The real Ionian base was on the sea; the Persian on the land.
Each side, in order to strike a decisive blow at the other, must strike
on that element on which the other was strong. This Persia did; and
this the Ionian Greeks failed to do in this campaign. The simple
result was that the Persian stood to win, the Ionian to lose.
The story of Ladé is one of the very few sections of the history of
the revolt in which Herodotus attempts anything of the nature of a
detailed narrative. It bears all the traces of a compilation from
various sources. It opens with a list of the fleet, giving not merely the
numbers of the contingents, but also the battle array. Chronologically
this latter feature is manifestly out of place, inasmuch as the battle
was fought some time after the gathering of the fleet.
The story of the events in Ladé itself prior to the battle is
noticeable for two elements which can hardly be attributed to the
same source. The despicable Ionian tyrant is made to appear more
despicable; and the Ionian insurgents are presented in a most
unfavourable light.
The list of ships contributed by the various
FLEET AT LADÉ.
States is as follows:⁠—
Miletus 80
Priene 12
Myus 3
Teos 17
Chios 100
Erythræ 8
Phokæa 3
Lesbos 70
Samos 60
353
The Persian fleet is said to have numbered 600.
The absence of Ephesus from the Greek list is noticeable. There
are other absentees of less note. If the contingent of Miletus, the
object of attack, be omitted, the number of ships supplied by the
states on the mainland amounts to only 43.
The smallness of this number is so remarkable that it cannot be
passed over without comment. One of two things must have
occurred. Either some of the Ionian towns had been reduced since
496, and the story of their reduction is part of the lost records of 495;
or the resistance was weakening, and the Greek cities were
withdrawing one by one from the struggle, after making their own
terms with the Persian. Of the two conjectures, the latter is, perhaps,
the more probable, as it would in a way justify the impression of
pusillanimity which Herodotus gives to the revolt, an impression
which, though on the whole unjustifiable, must have rested on some
partial basis. The tradition of the last act in the great tragedy, as
preserved in these renegade cities, was sure to be sinister; and from
them, or some one of them, Herodotus may have drawn information
which contributed to the formation of his own opinions.
The magnitude of the Ionian fleet which gathered at Ladé is in
itself sufficient evidence of the determination of the insurgents to
concentrate their effort on the sea. The Persian fleet was more than
half again as numerous; but it had already suffered two severe
defeats off Pamphylia and off Cyprus, and it showed a manifest
inclination to avoid a conflict. Herodotus does not mention the station
which it took up; but it was presumably somewhere near Miletus,
because some of the ex-tyrants of the Greek cities who were aboard
entered, at the instigation of the Persians, into communication with
their late subjects, with intent to detach some of the contingents from
the formidable armada. For the moment these intrigues met with no
success.
H. vi. 10.
Herodotus is evidently of opinion that even this
resistance to a proposal of treachery was an instance
39
of the wrong-headedness which the Ionians displayed throughout
the revolt.
It is very difficult to form a judgment as to the amount of historical
truth which is contained in the tale of the events which intervened
between this time and the actual battle. It is manifestly told with the
intention of presenting the Ionians in the worst possible light. This
people, which had already in the course of the revolt inflicted two
defeats by sea upon the Persians, is now represented as having
neither the power nor the will to practise the tactics of a sea-fight.
H. vi. 11. After the fleet had gathered at Ladé the Ionians
held meetings on land, at which the situation was
discussed. Among others who spoke was Dionysios, who
commanded the small Phokæan contingent.
“Our affairs,” he said, “are balanced on a razor’s edge,
Ionians, as to whether we are to be free men or slaves—
more than that, runaway slaves. Therefore, if you will now
have the will to bear hardships, toil for the moment will be
yours, but you will be able to overcome the foe and enjoy
freedom. If, however, you continue to display a lack of
fortitude and of discipline, I have no hope for you that you
will not pay to the king the penalty of revolt. Give ear to my
advice, and place yourselves in my hands. I promise you,
if the gods deal fairly by us, either that the enemy will not
give us battle, or that, if they do, will be badly beaten.”
To this advice the Ionians listened, and placed themselves for the
time being at his disposal. He accordingly practised them in
manœuvres every day, and especially in the manœuvre of cutting
the line, and kept them busy from morning to night. This they
endured for seven days. After that they refused to carry out the
orders of this “vagabond Phokæan, who provided only three ships.”
The language attributed to them is that of men
CONDEMNATION OF
THE IONIANS.
who, accustomed to lead a life of luxury, find
themselves in a situation of self-imposed
hardship, which they have not the courage to face. After five years of
resistance to the greatest power of their time, they are damned as
mere “boulevardiers” on the battle-field, “men who had no
experience of such hardships,” lacking the very elements of
courageous perseverance. The condemnation does not fall on the
population of those cities which are not represented in this last great
struggle for Ionian freedom, but on those who fought to the bitter
end. The extraordinary feature of the whole matter is that Herodotus
should have allowed such a tale to stand side by side with his
narrative of the battle, in which it appears that part of the Ionian fleet
fought with the most desperate courage.
The “Dionysios” story throws considerable light on the nature of
the sources for Herodotus’ history of the revolt. The personal
40
references to Dionysios may, like the subsequent reference to him,
be suggested by information as to his exploits obtained by the author
in some Greek city of Italy. But the intent of the whole story is
manifest. It provides an excuse for the conduct of those Samians
who deserted in the battle, to the tale of which it serves as a preface.
It is not merely a story of Samian origin, but a version to which
currency was given by certain persons in Samos, who found it
necessary to invent some defence for an act of cowardice for which
41
the facts themselves provided no excuse.
The introduction into the story of what is almost certainly an
anachronism, the manœuvre of “cutting the line,” is, however, a
graphic touch of the historian’s own, suggested to him, like the
reference to Kythera in the Persian debate after Thermopylæ, by the
incidents of the Peloponnesian war.
It is a strange tendency this, which the father of history now and
again displays, to introduce into his narrative a page or two of matter
which is conspicuously refuted by his general history. He is far too
honest to distort the story of events in accordance with his own
views; but he again and again, especially in the case of the revolt,
yields to the temptation of introducing evidence from manifestly
partial and contaminated sources, simply because it happens to
agree with his own judgment on the general course of events.
Of the origin of the story of the actual battle there can be but little
question. It is also a Samian version. But, even so, it is not simple in
its elements. The behaviour of the two sections of the Samian
contingent in the battle rendered it certain that two very different
versions of the fight would survive in Samos,—one of them the
creation of those who were faithless, and the other that of those who
were faithful to the Ionian cause. Herodotus’ account contains
features borrowed from them both. This oft-repeated characteristic of
his history is in no sense deplorable. It is essentially the
characteristic of his work which renders that work most valuable at
the present day, in that, by reason of it, the contemporary evidence
is preserved in the form in which he found it.
The truth with regard to the state of affairs in the Ionian fleet
before Ladé is, in all probability, that counsels were greatly divided
on the details of the course to be pursued in the battle which was
imminent. On this occasion, as on previous occasions, the lack of a
single directing mind made itself felt. There was no one in supreme
command. Even a Eurybiades, not gifted with the ability to devise a
great design, but possessed of a common-sense judgment which
would have enabled him to decide between the plans suggested by
others, might have saved the situation.
This lack of leadership, and consequent lack of unanimity is the
only excuse which can be brought forward for the doubly
treacherous conduct of the Samians.
BATTLE OF LADÉ.
Herodotus admits all the evidence for their
defence; but he does not exclude the damning evidence against
them. This is present not merely in the matter but in the form of the
history of the battle. Despite the fact that the grounds of their
apology were in accord with his own general views, he is not wholly
convinced that they constituted a valid excuse for their conduct on
the present occasion.
H. vi. 13.
“The Samian commanders,” he says,
“seeing what was taking place among the
Ionians, and their lack of discipline, proceeded to accept
the proposal which Æakes, the son of Syloson, had kept
sending them at the bidding of the Persians, calling on
them to desert the Ionian league. It appeared to them also
that it was impossible to overcome the resources of the
king, because they knew well that if the present fleet were
defeated another would come, five times as large.
“Seizing, then, upon this excuse, so soon as they saw
that the Ionians were unwilling to make a fight of it, they
thought it to their advantage to save their temples and
their property.”
The Æakes mentioned was one of the hated Ionian tyrants whom
Aristagoras had deposed at the beginning of the revolt. Herodotus
does not comment on his connection with the matter; but it is certain
that the part which he played in it would weigh heavily against the
Samian traitors in the balance of the historian’s judgment on their
act.
H. vi. 14.
In giving his account of the battle he suffers, as he
42
himself says, from a lack of reliable information.
Matter is, however, introduced which shows plainly that he had heard
at Samos a version of the story told from a point of view directly
opposed to that of the tale of events in the previous chapters, and
that this version was supported by inscriptional evidence existent in
his own day.
“When, therefore, the Phœnicians advanced to the
attack, the Ionians proceeded to put out against them with
43
their ships in column, But when they approached one
another, and joined battle, I am not able to say with
certainty which of the Ionians were cowardly or brave in
the sea-fight, for they cast the blame on one another. The
Samians are said to have set sail at this moment and to
have left the line of battle, with the exception of eleven
ships, and to have gone off to Samos, in accordance with
their agreement with Æakes. The captains of these eleven
vessels remained and fought, disregarding the orders of
the commanders. The Samian commonwealth, in
consequence of this act of theirs, voted that a pillar should
be set up in their honour, with their personal and family
names inscribed upon it, in that they had been brave men:
44
and this pillar is in the market-place.
“The Lesbians, seeing those next to them in the line in
flight, followed their example; and in like manner most of
the Ionians did the same. Of those who remained in the
battle, the Chians suffered most severely, for they made a
brilliant fight of it, and showed no cowardice. They
provided, as has been already said, 100 vessels, and forty
picked citizens on board each, serving as marines.
Though they saw the majority of the allies deserting, they
thought it not right to imitate their cowardice, but, left alone
with a few allies, they went on fighting, using the
manœuvre of cutting the line, until, after capturing many of
the enemy’s vessels, they had lost most of their own.”
Such of their vessels as were in a condition to do so, made off to
Chios; those which were seriously damaged were run ashore at
Mykale, whence their crews proceeded to make their way homeward
by land. On entering Ephesian territory at night, however, they
chanced upon the women celebrating the Thesmophoria, and, being
mistaken for robbers, were attacked by the Ephesians, and some of
them, at least, were killed.
This last incident may admit of various explanations; and it may
be doubted whether the action of the Ephesians was wholly due to
error. The attitude of this city at this time excites suspicion.
But the rest of the account of the battle
DIONYSIOS OF
PHOKÆA.
bears the impress of truth. Anti-Ionian or not,
Herodotus cannot withhold his admiration from those who fought to
the bitter end.
One detail may be inferred from its general incidents. The ease
with which both the Samians and the other allies got away, and with
which the Chians retreated after the fight, suggests that the Greek
fleet at the beginning of the battle was north of the Persian.
Dionysius of Phokæa is the only hero of it whose name has come
down in story. That old sea-dog, the very prototype of the seamen of
the days of Elizabeth, had no mind to return to Phokæa and share
the slavery of whatever small remnant of its inhabitants had either
remained in their old home, or had returned thither from Corsica.
With his three ships he had, in the course of the fight, taken three of
the enemy’s vessels; and now he sailed off, not in any cowardly
flight, but with the determination to “singe the King of Persia’s beard”
by an unexpected raid into his home waters. To Phœnicia he went,
and there fell in with certain merchant ships, which he disabled and
plundered; and then, laden with spoil, set sail for Sicily, where he set
up as a pirate at the expense of the Carthaginian and Tyrrhenian
traders of those seas. Doubtless the Greek cities of Italy appreciated
to the full so valuable an ally in trade competition, and from them
Herodotus learnt the history of the last days of the fierce old
adventurer. The world is poorer in that further details of his life have
not survived. Would that some Sicilian writer had taken down his
story from his own lips! It might have been one of the greatest tales
of adventure in literature.
There must have been many another who fought a good fight for
liberty. They had the misfortune to have their deeds recorded by men
less brave than they. But even amid the intense partiality of the
history of the time the truth shines forth that, owing to the courage
which they displayed, the story of the revolt is one of the glorious
pages in the history of the Hellenic race. The fault of those men who
persevered to the bitter end was not lack of courage, but lack of the
perception that nature had so placed them in the world that their
struggle against the great empire was from its very outset a
desperate, a hopeless venture. It is not possible to suppose that,
without the energetic help of the European Greek, the revolt could
have ended otherwise than as it did; it may even be doubted
whether, even with help from beyond the Ægean, the struggle could
have been maintained against the enormous resources of Persia, as
yet unimpaired by the disasters of the great war of 480 and 479.
Even after that war, the energy and strength of Athens could not
maintain more than an uncertain hold on the cities of the continent.
But the revolt had saved Greece.
The great blow levelled against her must have fallen in the first
decade of the fifth century; and, had it done so, it would have fallen
upon a Greece but ill-prepared to meet it. The struggle would
doubtless have been a fierce one, but it would have been waged on
the part of the Greeks without the aid of that factor which was
decisive in the great struggle of ten years later—the great Athenian
fleet.
The revolt had severely taxed the resources of the Empire. It took
Persia six years to suppress it, and in this time she lost two fleets
and one great army with its generals, besides the losses incurred in
successful operations. It resulted that, though she did make two
efforts in the years immediately following the revolt to gain a footing
beyond the Ægean, those efforts were not of a nature which, judged
in the light of knowledge after the event, could have attained any
measure of success. She was unable at this time to set on foot an
expedition adequate to the greatness of the undertaking.
It is impossible, on the evidence, to say that the struggle was
carried on with a unanimity of courage on the part of all the Ionian
towns; but it is plain that this aspect of the history of the time has had
undue weight in the judgment formed by Herodotus.
H. vi. 18.
The end was near. Miletus, the heart and soul of
the revolt, was besieged by sea and land. The walls
were undermined, and all sorts of siege engines were employed.
Finally, some time in the late summer or
FALL OF MILETUS.
autumn of 494, the city fell. The fate of the
population was a piteous one. The great majority of the male
inhabitants were massacred. The women and children were
enslaved, and carried captives to Susa. They and the remnant of the
male population were placed in a settlement on the Persian Gulf,
near the mouth of the river Tigris.
It is very difficult to estimate the loss which civilization has
suffered by the destruction of this great city, which had been, up to
the very time of its destruction, the foremost in the Hellenic world. It
was not merely in the front rank in Greek commerce; it was also an
intellectual centre unrivalled among the cities of the age. Whether it
could ever have developed a period of literary brilliance equal to that
of the Athens of the later part of this century, must remain a matter of
speculation. It had a long start in the intellectual race. The wide
interest of its material relations called forth a corresponding breadth
of interest in literary speculation of various kinds; and the world
would certainly have been enriched, had it possessed an Asiatic
Greek literature parallel to that of European Greece. Difference of
environment and difference of political circumstances would have
produced a literary development on different lines; and the literature
itself could not have failed to display one side of the many-sidedness
of the Greeks, which is lost to the present world, save for a few
fragments, which point to a promise of future greatness.
H. vi. 21.
At Athens the fall of the great city created more
than a momentary impression. Phrynichos composed
a drama on the subject which aroused so bitter a sense of loss in the
mind of the Athenians that they punished the dramatist by a fine of a
thousand drachmas. It is possible that self-reproach was mingled
with regret. The desertion of 498 was so sudden, and is, in certain
respects, so unaccountable, that it may well have provoked
considerable feeling even in Athens itself.
Herodotus draws a contrast between the emotion of Athens and
the apathy of the Sybarites. When Sybaris was destroyed by Kroton
about the year 510, the whole Milesian population had mourned the
loss of their old commercial friend.
The last twenty years had been fateful in the history of Greek
trade. Sybaris, Chalkis, and Miletus—three of the greatest names in
the history of Greek commerce—had successively fallen; and their
disappearance from the stage of the commercial world must have
greatly modified that obscure but powerful factor in Greek history. It
will be a matter for later consideration whether the disappearance of
these competitors, especially from the western trade route, had not a
powerful influence in shaping the events of the later half of the
century.
Of the individual fortunes of the rest of the Asiatic Greek cities,
Herodotus says but little. Among the Samians, the divided counsels
in their contingent at Ladé seem to have given birth to such bitter
dissensions that a section of the population which had remained
loyal to the revolt left the island and set sail for Sicily, whence an
invitation had come from the people of Zanklé, calling such Ionians
as would to settle at Kale Akte on the north coast of the island. Their
45
adventures are related by Herodotus. It is not necessary to follow
them thither. Suffice it to say that the gross treachery of their conduct
to their would-be hosts upon their arrival there affords one of those
painful and striking examples of the co-existence in the Greek race
of great virtues and great defects.
H. vi. 25.
Æakes, the tyrant who had negotiated the treachery
at Ladé, as a reward for his services on that occasion,
was reinstated in Samos by the Phœnician fleet. The city and its
temples were left untouched.
“Immediately after the capture of Miletus,” says Herodotus, “the
Persians got possession of Caria, some of the cities submitting
voluntarily, and others being reduced by force.”
The part played by Caria, as described in the narrative of the
revolt, is quite incomprehensible. What had she been doing during
the time that had intervened since the great defeat of the Persians
on the Pedasos road? The interval cannot,
SUBJUGATION OF
CARIA.
upon any calculation from the facts mentioned
by Herodotus, have amounted to less than two
years. Were the Carians during all this time inactive, sullenly
awaiting their fate? Their story during these years is a lost chapter in
history.
It would seem unlikely that Herodotus could not have obtained
any information with regard to the course of events in the land
immediately bordering on the territory of his own native town. The
only possible conjecture is that his reference to the reduction of
Caria as having taken place after that of Miletus, applies to its
complete subjugation, and that the process had been going on for
some time. It has already been suggested that the inactivity of Caria
was due partly to its resistance having been undermined by Persian
diplomacy in the period following the great defeat; and it may be that
those towns which submitted voluntarily had been gradually
detached from the insurrection by offers of favourable terms from
Artaphernes.
H. vi. 26.
Histiæus plays the chief part in the last scene of the
drama of the revolt. Whenever this mysterious man
appears upon the stage he brings mystery with him. He is still at
Byzantion when the scene opens. He has been there for at least a
year. But the strange feature of the matter is that, though he has
been there so long, and though during all that time he has been
committing acts of piracy (sic) against the Ionian traders, those
simple-minded folk continue to send their vessels into the inevitable
trap.
H. vi. 26.
His Lesbians are still with him, presumably the
crews of the eight ships the Mytilenians had granted
him. And yet while all these strange proceedings are going on at
Byzantion, and while their own people are taking part in them, these
very Mytilenians send seventy vessels to Ladé! Byzantion was less
than two days’ sail from them, and with half that number of vessels
they could have put a stop to what was going on there, had they had
the will to do so. They must have been satisfied that Histiæus was
acting in their interest; and had that consisted in the perpetration of
piratical acts against their allies, it is strange that they should have
thought it their interest to join those allies at Ladé. They played,
indeed, a coward’s part there, but not without excuse.
The evidence, though anything but conclusive, suggests the
suspicion that Histiæus was acting in the interest of those cities who
persevered in the revolt against those other Greek cities who had
made, or had sought to make, terms with the Persian.
His proceedings after he had received the news of the fall of
Miletus are less obscure in motive than his doings at Byzantion. His
position in the Hellespontine region had certainly developed in the
course of the year during which he had been there.
He left his affairs in charge of a certain Bisaltes of Abydos. His
first objective was Chios. Thither accordingly these “beggars of the
sea,” commanded by this broken adventurer, made their way. Driven
to desperation, he and they had made up their minds to one great
final effort to save whatever could be saved. It would seem, too, that
Histiæus had a plan by which he thought this might be
accomplished. The only possible explanation of his conduct, on the
extant evidence, is that he once more turned his thoughts to Thrace,
and sought to establish on the Strymon a rallying-point for the
irreconcilables among the insurgents. He sought to resume in a
modified form a design he had been forced to lay aside nearly twenty
years before.
But it may be urged: If this was so, why did he direct his first
efforts against Chios?
Did he go to Chios with any hostile intent at all? Were the
hostilities there forced upon him by the deep distrust of him which
the Chians entertained? The evident and well-founded contempt of
Histiæus, which Herodotus felt on general grounds, has influenced
his tale of what happened at Chios. He deplores alike the fate and
folly of these Chians—their fate, in that suffering was added to their
sufferings; their folly, in that they had brought these sufferings upon
themselves by joining in the revolt, and by persevering in it to the
bitter end.
Yet even so, his story shows that Histiæus’
HISTIÆUS AND
CHIOS.
action with regard to them was capable of at
least two interpretations:
H. vi. 26.
“Affairs in the Hellespont he committed to the
charge of Bisaltes, the son of Apollophanes, of
Abydos, while he himself, accompanied by the Lesbians,
46
sailed to Chios, and engaged with a Chian garrison
which would not admit him, at a place in the Chian territory
called the Hollows.”
This seems to imply that he had expected the Chian garrison to
receive him.
“Of these he killed many, and, from a base at Polichne,
in Chian territory, he with the Lesbians, got the mastery of
the rest of the Chians, who were in evil plight after the
naval battle.”
Apart from the fact, already noticed, that Histiæus seems to have
expected a peaceable occupation of Chios, it is remarkable that
there is no mention of any bloodshed, save in the case of attack of
the one garrison.
The colouring which is given to events by the tale of the organized
attack on Chios from a base at Polichne, is evident. The whole intent
of it is to represent the expedition of Histiæus as hostile to the
Chians, and to emphasize the despicable behaviour of the various
sections of the insurgents to one another when their fortunes had
become desperate. Æolian attacks Ionian, and Ionian resists Æolian.
And yet, in spite of this, Ionian joins Æolian in that attack on Thasos
which immediately succeeds this period of alleged hostility.
But the story is not merely inconsistent with itself; it is hopelessly
inconsistent with such circumstances of the time as may be gathered
from Herodotus’ own evidence.
What conceivable object had Histiæus and these Lesbians in
attacking Chios at a time when its reconquest by the Phœnician fleet
could not be long deferred? Histiæus may or may not have been a
scheming knave, but there is no reason to suppose that he was a
witless man, unable to gauge the impossibility of maintaining Chios,
or any of the islands on the Asian coast, after the disaster at Ladé.
Then why did he go to Chios? The answer to this question is
dependent on the answer to a further question: Why, after occupying
Chios, did he immediately attack Thasos?
Only one explanation of his conduct seems consistent with the
circumstances of the time. The days of the revolt were numbered. A
terrible retribution was to be apprehended. There must have been
hundreds, perhaps thousands, of refugees on the Ionian coast of
Asia, seeking for some shelter from the coming storm; and whither
would they turn? To the islands first, as being safer than the
mainland, with intent to secure time for escape over seas. Chios was
the refuge to which these refugees would look in the first instance.
Samos was anxious only for itself. Lesbos was farther from the
centre of things. Chios was the natural rallying-point.
It was under these circumstances that Histiæus turned to Chios
first after leaving the Hellespontine district. His action need not be
attributed to philanthropic motives. It was at Chios that he would find
any number of desperate recruits, ready for any venture on which he
might propose to lead them; and he had such a venture planned in
his mind.
His past experiences with the Chians had been unfortunate. But
he had in the past managed to persuade them of his good faith
towards the revolt; and why should he not be able to do so now?
The Chians were unprepared for his coming, and his landing was
resisted. He accordingly withdrew to Polichne. This place lay near
47
Klazomenæ, and commanded from the land side the peninsula off
which Chios lies. Herodotus says that he used
HISTIÆUS AT
THASOS.
the place as a base of operations against the
Chians. The improbability of his having, at this
juncture of affairs adopted an attitude of hostility towards the Chians,
and, above all, of his having deliberately entered upon operations
against them at a time when the arrival of the Phœnician fleet might
be expected, is so great, that it is impossible to accept the statement
as a reliable record of events. Later tradition may well have
interpreted his proceedings at Polichne in the light of the unfortunate
incident with the Chian garrison. Whether depressed or not by the
defeat at Ladé, it is beyond imagination that this powerful island-
state should have succumbed to an attack from such a force as
Histiæus could have brought with him. It is infinitely more probable
that he withdrew to Polichne in order to be able to explain his attitude
to the Chians before further collision took place, and that he did
persuade them of the bona fides of his intentions.
His next proceedings throw considerable light upon those
H. vi. 28.
intentions. Having got the Chians to his side, he
proceeded to attack the Island of Thasos, taking with
him “many of the Ionians and Æolians.”
There can be no doubt as to the general reasons which prompted
this attack. Thasos had considerable possessions on the lower
Strymon.
The particular reasons may be matter for conjecture. It is, at least,
conceivable that the Thasians had the strongest objection to the
establishment of a new power in a region in which they had so much
at stake, in the shape of those gold-mines which brought them such
enormous wealth; and that Histiæus found it necessary to subdue
them, before he tried to carry out his plans on the continent.
Had the Thasians participated directly or indirectly in the disaster
which befell Aristagoras?
Be this as it may, Histiæus was only carrying out in a new form,
and under conditions more favourable to himself, a policy he had
attempted to initiate years before, the initiation of which had caused
his removal to Susa. He was now backed up by a number of
desperate men, ready for any venture which might save them from
the hands of the Persian. But time was all-important. The Phœnician
fleet was at the moment engaged in the reduction of such Carian
towns as still resisted; but its arrival in the North Ægean could not be
long deferred.
It was, no doubt, owing to the resistance of Thasos that the plan
miscarried. While he was besieging the place, news arrived that the
Phœnician fleet was moving northward. This being so, it was quite
certain that the Æolians in his force would insist on an attempt being
made to rescue the Lesbians, if not Lesbos. So to Lesbos Histiæus
went.
H. vi. 28.
He arrived there only to find that the food supplies
of the island, exhausted probably by the influx of
refugees, were insufficient to support his army. So he crossed over
with it to the mainland, making Atarneus his base, and intending to
operate from it and seize the harvest-produce of its neighbourhood,
and of the valley of the Kaïkos river.
Here he was attacked by a large Persian army under Harpagos. A
large part of his force was destroyed, and Histiæus himself was
captured.
H. vi. 29. “In the battle between the Greeks and

Persians at Malene in the country at Atarneus,
the Greeks resisted for a long time, but the cavalry being
afterwards launched against them fell upon the Greeks.
From that moment the attack became simply a cavalry
affair. On the Greeks being put to flight, Histiæus, hoping
that he would not perish at the hands of the king owing to
his present transgression, conceived such a desire for life,
that when in his flight he was overtaken by a Persian, and
being overtaken was about to be stabbed to death by him,
using the Persian language, he declared himself to be
Histiæus the Milesian. If he had, when he was captured,
been taken forthwith to King Darius, my belief is that he
would have suffered no harm, but that the king would have
freely forgiven him.”
But so it was not to be. The great Persian officials had no
intention of giving their old enemy a chance of his life. When
Harpagos brought him to Sardes, Artaphernes had him executed
and sent his head up to Susa. Greek tradition
HISTIÆUS.
represented Darius to have treated the poor
remains with honour, as being those of a man who had been a great
benefactor to the Persians and their king.
Histiæus has come down in story as the arch-villain of his time.
He was the most contemptible member of a hated class, as the men
thought who created the story of his life, and as Herodotus, who
implicitly copied the picture which they drew of him, thought also.
He cannot be accounted fortunate in his biographer. The shadows
of the picture are so deep that the true lineaments of the man cannot
now be clearly discerned. But he who tries to play a double part, and
fails in the attempt, as Histiæus did, is not likely to occupy an
honourable place in history. He seems to have been of great and
selfish ambition, without the capacity to form a judgment as to the
means requisite to carry it out, and without any scruple as to the
means he did adopt. He figures consequently as a scheming but
somewhat futile villain. He had made up his mind that his main
endeavour must be to win the confidence of Darius, and that, if he
won this, he could afford to ignore the great officials. He forgot how
far a cry it was from Susa to Sardes. He wished at all costs to rule
the Asiatic Greek—independent of Persia, if he could; under Persia,
if he could not; but not under any satrap at Sardes or elsewhere. His
plan, well conceived, but prematurely executed, of gaining a point
d’appui in Thrace, gave away the whole design at its very inception.
There followed years of exile at Susa. He returned to the coast to
find the revolt undecided. He had, or thought he had, two alternative
cards to play: either to help in the suppression of the revolt, and to
make Darius believe that he had been mainly instrumental in its
suppression, or to take the lead in the rising. But Artaphernes forced
his hand, and he had no alternative but to play his second card. It
might have been effective, had he been allowed to bide his time; but
the premature display of it spoiled his whole game,—in fact, the
Greeks would have none of him.
And in the last scene of all, at Chios, Thasos, and Lesbos, his
curse is still upon him. He again miscalculated the means necessary
to effect his design in the limited time within which it could possibly
be successful. His cleverness was greater than his ability. He
possessed the finesse of a schemer, but lacked the practical reason
of the man of action.
His capture must be attributed to the spring of the year 493,
inasmuch as his army was engaged in reaping the spring crops in
the neighbourhood of Atarneus at the time at which it was attacked
by Harpagos.
The rest of the tale of the revolt is soon told.
The Persian fleet, having wintered at Miletus, proceeded in the
spring of 493 to reduce the island states. Chios, Lesbos, and
Tenedos fell into their hands. Herodotus reports that they “netted”
these islands, that is to say, swept them from end to end with a line
of men with joined hands stretching from sea to sea. If the story be in
any sense literally true, it probably means that the Persians were
anxious to get hold of prominent refugees. Nothing is said as to what
they did with those they captured.
H. vi. 32.
Presumably the reduction of the continental cities
was proceeding at this same time. If the list of ships at
Ladé be any criterion, it would seem as if but few of them remained
to be reduced. Those that did remain were treated with severity.
Children of both sexes were carried away up country, and the cities
with their temples were burnt to the ground.
This was the end of the revolt in Asia.
The operations which followed in Europe, though aiming at the
subjugation of revolted districts, have a more intimate historical
connection with their sequel than with the tale of the revolt itself.
CHRONOLOGY OF THE REVOLT.

500–499
W. Aristagoras proposes the Naxos scheme to
Artaphernes.
Artaphernes communicates the proposal to
Darius.
Sp. Gathering of Ionian fleet and of the expedition
generally.
S. Siege of Naxos.
A. Failure of siege.
Meeting of Greek conspirators.
Deposition of tyrants.
499–498
W. Aristagoras at Sparta and Athens.

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References Chapman, C. R., & Vierck, C. J. (2017). The transition of acute

H. vi. 29. “In the battle between the Greeks and

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