Cancer Pain
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Editors
Magdi Hanna, MBBCH, FCA Zbigniew (Ben) Zylicz, MD, PhD
Analgesics and Pain Research Unit Department of Research and Education
(APR LTD) Hildegard Hospiz
Beckenham Basel
Kent Switzerland
United Kingdom
ISBN 978-0-85729-229-2 ISBN 978-0-85729-230-8 (eBook)
DOI 10.1007/978-0-85729-230-8
Springer London Heidelberg New York Dordrecht
Library of Congress Control Number: 2013945729
© Springer-Verlag London 2013
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To Kate, Sam, Jonathan, and Daniel for their
everlasting support.
Magdi Hanna
In memory of my Mother who died many years ago
of cancer, she was my best teacher ever.
Zbigniew (Ben) Zylicz
Preface
During the professional life of the editors, and most of the authors, cancer
pain management has undergone radical improvements. We have seen regular
opioids adopted as the norm, and oral administration has become the pre-
ferred route of administration despite early resistance from medics and the
public.
However, in spite of these improvements, recent studies demonstrate that
one-third of adult patients with cancer who are in active therapy and two-
thirds of patients in the advanced stages of the disease still suffer from
significant pain.
To face this challenge, we have been forced to develop a fresh understand-
ing of the dynamic pathophysiology of cancer pain, and it has become clear
that a modern and more comprehensive model for cancer pain management is
necessary.
Mechanism-based and multimodal combination therapies (including inter-
vention techniques) that are tailored to the needs of the individual should
prove the most efficacious techniques in the fight against cancer pain. The
aim is, as ever, to optimise pain relief, minimise adverse effects of the treat-
ment, and improve long-term outcome.
Improved survival rates among cancer sufferers, a result of enhanced anti-
cancer therapy, have had the paradoxical effect of creating a significantly
more complex pain syndrome. This has added a new clinical challenge for
patients and physicians, and the chapters of this book are aimed squarely at
confronting these issues. We have placed specific emphasis on the modern
challenges that cancer care teams face in the twenty-first century and aim to
provide an up-to-date outline of the current thinking in the treatment of can-
cer pain.
We are deeply indebted to all those who contributed to this book despite
the pressure of their work and would like to acknowledge our gratitude to our
publishers for their constant help and assistance.
Beckenham, Kent, UK Magdi Hanna, MBBCH, FCA
vii
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Magdi Hanna and Zbigniew (Ben) Zylicz
2 Epidemiology of Pain in Cancer . . . . . . . . . . . . . . . . . . . . . . . . . 5
Irene J. Higginson, Fliss E.M. Murtagh, and Thomas R. Osborne
3 Recent Advances in Cancer Treatment . . . . . . . . . . . . . . . . . . . 25
M.J. Lind
4 Pharmacogenetics of Pain in Cancer . . . . . . . . . . . . . . . . . . . . . 37
Pål Klepstad
5 Mechanisms in Cancer Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47
Jerzy Wordliczek and Renata Zajaczkowska
6 Preclinical Cancer Pain Models . . . . . . . . . . . . . . . . . . . . . . . . . 71
Joanna Mika, Wioletta Makuch, and Barbara Przewlocka
7 Pain Assessment, Recognising Clinical Patterns,
and Cancer Pain Syndromes. . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
Malgorzata Krajnik and Zbigniew (Ben) Zylicz
8 Opioids, Their Receptors, and Pharmacology . . . . . . . . . . . . . 109
R.A.F.J. D’Costa and Magdi Hanna
9 Critical Appraisal of the Breakthrough
Pain in Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
Zbigniew (Ben) Zylicz
10 Opioid-Induced Hyperalgesia . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Jakob Sørensen and Per Sjøgren
11 The Non-Pharmacological and Local Pharmacological
Methods of Pain Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
Remigiusz Lecybyl
12 New Drugs in Management of Pain in Cancer . . . . . . . . . . . . . 153
Marie Fallon
13 Neuropathic Component of Pain in Cancer . . . . . . . . . . . . . . . 165
Jung Hun Kang and Eduardo Bruera
14 Noncancer-Related Pain in Daily Practice. . . . . . . . . . . . . . . . . 191
Zbigniew (Ben) Zylicz
ix
x Contents
15 Rehabilitation of Cancer Patients, a Forgotten Need? . . . . . . . 203
Roberto Casale and Danilo Miotti
16 Psychosocial Aspects of Cancer Pain . . . . . . . . . . . . . . . . . . . . 211
Marijana Braš and Veljko Ðorđević
17 Spiritual Care and Pain in Cancer . . . . . . . . . . . . . . . . . . . . . . . 221
Carlo Leget
18 Interventional Techniques in Cancer Pain:
Critical Appraisal. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
Vittorio Schweiger, Enrico Polati, Antonella Paladini,
and Giustino Varrassi
19 Access to Opioid Analgesics: Essential
for Quality Cancer Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
Willem Scholten
20 Challenges for Pain Management
in the Twenty-First Century . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
Mellar P. Davis
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
Contributors
Marijana Braš, MD, PhD (biomedicine) Department of Psychological
Medicine, University of Zagreb, School of Medicine, Centre for Palliative
Medicine, Medical Ethics and Communication Skills, Zagreb 10000, Salata 4
Eduardo Bruera, MD Department of Palliative Care and Rehabilitation
Medicine, University of Texas M.D. Anderson Cancer Center, Houston,
TX, USA
Roberto Casale, MD, PhD Department of Clinical Neurophysiology and
Pain Rehabilitation Unit, Foundation Salvatore Maugeri, Research and Care
Institute, Rehabilitation Institute of Montescano, Montescano, Italy
Mellar P. Davis, MD, FCCP, FAAHPM Department of Solid Tumor,
Taussig Cancer Institute, Cleveland Clinic Lerner School of Medicine,
Cleveland Clinic, Cleveland, OH, USA
R.A.F.J. D’Costa, FFARCSI Department of Anaesthetics, King’s College
Hospital, Denmark Hill, London, UK
Veljko Ðorđević, MD, PhD Department of Psychological Medicine,
University of Zagreb, School of Medicine, Centre for Palliative Medicine,
Medical Ethics and Communication Skills, Zagreb 10000, Salata 4
Marie Fallon, MBChB, MD, FRCP University of Edinburgh,
Western General Hospital, Edinburgh, UK
Department of Palliative Medicine, Edinburgh Cancer Research Centre,
Edinburgh, UK
Magdi Hanna, MBBCH, FCA Analgesics and Pain Research Unit
(APR LTD), Beckenham, Kent, UK
Irene J. Higginson, BMedSci, BMBS, PhD Palliative Care, Policy and
Rehabilitation, Cicely Saunders Institute, King’s College London, London, UK
Jung Hun Kang, MD Division of Oncology, Department of Internal
Medicine, Gyeongsang National University Hospital, Jinju, Gyeongnam,
South Korea
Pål Klepstad, MD, PhD Department of Intensive Care Medicine,
St. Olavs University Hospital, Trondheim, Norway
xi
xii Contributors
Malgorzata Krajnik, MD, PhD Palliative Care Department, Nicolaus
Copernicus University, Collegium Medium in Bydgoszcz, Bydgoszcz, Poland
Remigiusz Lecybyl, MD, PhD The Pain Management Unit,
University Hospital Lewisham, Lewisham, Kent, UK
Carlo Leget, PhD Ethics of Care, University of Humanistic Studies,
Utrecht, The Netherlands
M.J. Lind, BSc, MD, FRCP Academic Department of Oncology,
Hull York Medical School, University of Hull, Hull, Yorkshire, UK
Wioletta Makuch, MSc Department of Pain Pharmacology,
Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
Joanna Mika, PhD Department of Pain Pharmacology, Institute of
Pharmacology, Polish Academy of Sciences, Krakow, Poland
Danilo Miotti, MD Palliative Care and Pain Therapy Unit, Department of
Palliative Care and Pain Medicine, Fondazione Salvatore Maugeri – IRCCS,
Pavia, Italy
Fliss E.M. Murtagh, PhD, MSc, MRCGP, MBBS Palliative Care, Policy
and Rehabilitation, Cicely Saunders Institute, King’s College London,
London, UK
Thomas R. Osborne, MA, MBBS Palliative Care, Policy and
Rehabilitation, Cicely Saunders Institute, King’s College London,
London, UK
Antonella Paladini, DR Department of Anaesthesiology, Intensive Care
and Pain Medicine, Ospedale San Savatore, University of L’Aquila – Italy,
Via Vetoio, 1 – Coppito, L’Aquila, Abruzzo, Italy
Enrico Polati, DR Department of Anesthesia and Intensive Care,
Pain Therapy Centre, Policlinico G.B. Rossi, Verona, Italy
Barbara Przewlocka, PhD Department of Pain Pharmacology,
Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland
Vittorio Schweiger, PhD Department of Anesthesia and Intensive Care,
Pain Therapy Centre, Policlinico G.B. Rossi, Verona, Italy
Per Sjøgren, MDSci Section of Palliative Medicine,
Department of Oncology, Rigshospitalet Hospital,
Copenhagen, Denmark
Jakob Sørensen, MD Section of Palliative Care, Department of Oncology,
Odense University Hospital, Odense C, Denmark
Giustino Varrassi, DR, PhD, FIPP Asl Teramo – National Health Care
Service, Teramo, Abruzzo, Italy
Contributors xiii
Jerzy Wordliczek, MD, PhD Department of Pain Treatment and Palliative
Care, Jagiellonian University Medical College, Krakow, Poland
Department of Anaesthesiology and Intensive Care, University Hospital,
Krakow, Poland
Renata Zajaczkowska, MD, PhD Department of Anaesthesiology,
Intensive Care and Pain Treatment, Province Hospital, Rzeszow, Poland
Institute of Obstetrics and Emergency Medicine, University of Rzeszow,
Rzeszow, Poland
Zbigniew (Ben) Zylicz, MD, PhD Department of Research and Education,
Hildegard Hospiz, Basel, Switzerland
Introduction
1
Magdi Hanna and Zbigniew (Ben) Zylicz
Abstract
Chronic pain is an extremely prevalent and complicated symptom in
patients with active cancer. It is a complex and dynamic syndrome that
encompasses multiple pathophysiological mechanisms and one that
demands an up-to-date and flexible therapeutic toolkit.
Keywords
Cancer pain • Comprehensive strategy • Evidence-based therapy •
Multidimensional • Cancer survivors
In order for physicians and cancer care teams to There have been some fundamental improve-
meet the challenges of cancer pain, a multidimen- ments in the field of cancer pain in the last few
sional and comprehensive strategy is required. decades. The creation of palliative care, improved
This strategy should combine critical assessments recognition of the burden on individuals and their
of the pain with a balanced evaluation of the families suffering from the syndrome, and the
underlying disease. Treatment should be centred liberalisation of the use of opioids for manage-
on an evidence-based therapy that employs ment of pain by an increasing number of govern-
specific analgesic intervention within an individ- ments and health providers have all helped to
ualised, tailored-to-the-patient, plan of care. This improve our understanding and response to the
plan should be “future-proofed” for any predicted problem.
progression of the disease and designed to remain Nevertheless, recent reviews state that large
appropriate throughout the course of the illness. numbers of patients are still suffering from can-
cer pain, and despite rapid increases in opioid
M. Hanna, MBBCH, FCA (*) consumption (at least in the developed world
Analgesics and Pain Research Unit (APR LTD), [1]), the percentage of those suffering from can-
62 Park Road, Beckenham, Kent BR3 1QH, UK cer-related pain has not been reduced
e-mail: [email protected]
significantly over the course of the last 40 years
Z. Zylicz, MD, PhD [2]. On a global scale, cancer pain is barely con-
Department of Research and Education,
Hildegard Hospiz, St. Alban Ring 151,
trolled, and almost 80 % of the world cancer
Basel 4020, Switzerland population receives little or no pain medication
e-mail: [email protected] at all.
M. Hanna, Z. Zylicz (eds.), Cancer Pain, 1
DOI 10.1007/978-0-85729-230-8_1, © Springer-Verlag London 2013
2 M. Hanna and Z. Zylicz
Pain is not only limited to populations with new pain management challenges in selected
active cancer but can persist in cancer survivors chapters of this book.
(patients cured of cancer or living with cancer as Dame Cecily Saunders, who succeeded in pro-
a chronic illness). This group of patients is viding a simple scheme for the employment of
increasing in numbers as a result of the significant morphine in the treatment of pain, also recognised
improvements in cancer survival rates. This pres- the significant contribution of the psychological,
ents new and different challenges to physicians, social, and spiritual aspects to the intensity of a
and we must work to identify the appropriate patients’ suffering [4]. This is the concept known
therapeutic framework and best practices for this as “Total Pain.” While these aspects do not fit into
heterogeneous group [3]. our pharmacological paradigm of cancer pain,
In order to improve the outcome for patients they are nevertheless vital in successfully produc-
suffering from chronic pain associated with can- ing beneficial outcomes for patients. Although
cer, it is clear that a progressive framework, one this concept was proposed by Dame Saunders, it
that meets the individual patient needs, as well as was never fully accepted into the canon of mod-
being fully evidence based, is required. ern medicine and, as a consequence, spiritual care
With this book, we hope to provide to the workers remain the unsung heroes of the manage-
reader a comprehensive, up-to-date understand- ment of pain in cancer patients. It is interesting to
ing of the complex demands that pain in cancer note that in some countries spiritual care is inte-
can make on a patient, their families, and the grated into the total and holistic care for cancer
medical teams that care for them. We aim to patients, with beneficial outcomes.
highlight the importance of critical and continu- Ultimately, this book is created on the under-
ous assessment of the many dynamic pain syn- standing that there is no such thing as “Cancer
dromes associated with cancer as well as Pain” but rather a complex syndrome of a variety
providing the therapeutic modalities available. of mechanisms that contribute to “pain in can-
We have also aimed to highlight the necessity cer.” As a consequence of this, we cannot
for psychological, emotional, and rehabilitation approach treatment with one modality.
therapies. While opioids remain the mainstay of pain
In the last four decades, our understanding of treatment, they should never be employed alone.
pain in cancer has increased dramatically. Each pain, and a single patient may experience a
However, the ability of the system to react to this number of pains, should be addressed separately
understanding and absorb the new ideas associ- [5]. The idea of this being that in the employment
ated with it appeared extremely limited. This of pharmacological (that includes adjuvant drugs)
seems especially so of the movement to keep as well as non-pharmacological treatments (that
patients in, or close to, their homes, and transfer- includes interventional techniques), we may min-
ring this new, modern knowledge of pain to front- imise the dose and therefore the long-term,
line treatment providers and care teams remains a adverse effects of opioids.
significant challenge. This approach is more complicated than the
To many, this new knowledge may appear WHO analgesic ladder [6] and will lead, in most
complicated and confusing. It may even appear patients, to polypharmacy, but with the overall
that patients are suffering more pain now than aim of optimising pain control and improving
they were in recent past. It is important to remem- overall outcome for patients.
ber that, in the past, patients were suffering As a consequence of accepting that our system
because of undertreatment and the scarcity of is now more complex, we will need to redefine the
appropriate drugs. Now, patients are suffering roles of specialists, supporting physicians, and
because they are living longer and developing nurses in primary care. We need a strong network
new, previously unknown pains, as well as previ- of passionate professionals who learn from each
ously undiscovered issues related to the long- other and, most importantly, appreciate and react
term use of opioids. We hopefully address these to the changing medical landscape around us.
1 Introduction 3
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