Am j hosp palliat care 2004-davis-137-42

Abstract
Pain is one of the most commonly
experienced and feared symptoms of
advanced cancer. Most cancer patients
experience pain, usually of moderate to
severe intensity, and most also have a
number of distinct pains. The most com-
mon type of pain is related to bone
metastases. Neuropathic pain occurs in
one-third of patients, alone, or as a mix
of nociceptive and neuropathic pain.
The failure to manage pain proper-
ly is due to several factors. In develop-
ing countries, it is likely to be related
to geography and limited resources.
Legal restrictions also present barri-
ers. In developed countries, failure to
manage pain properly is usually relat-
ed to a “disease” rather than a “symp-
tom” model of care, which minimizes
symptom management. Other factors
include lack of physician education and
failure to follow existing guidelines.
Patients fear addiction, drug tolerance,
and side effects. Despite adequate re-
sources, pain is still undertreated.
Key words: pain, opioids, pallia-
tive care, epidemiology, cancer
Introduction
Pain is an unpleasant sensory or
emotional experience associated with
actual or potential tissue damage or an
experience described in terms of such
damage.1
Even though pain is associat-
ed with tissue destruction, pain intensi-
ty is not proportional to the type or
extent of tissue damage. Pain is modu-
lated at various sites within the nervous
system, including the dorsal horn, peri-
aqueductal gray, brain stem, medial
thalamus, and anterior cingulate
cortex.2
Pain is also influenced by past
experience, mood, and cognitive func-
tion. Therefore, pain perception is best
described as a biopsychosocial experi-
ence.3
Pain can be subdivided into: 1)
somatic pain, 2) neuropathic pain, and
3) visceral pain.4,5
The prevalence of
pain in cancer is governed by the type
of cancer, stage, location of metasta-
sis, and comorbidity.6
Incident pain,
tenesmus, colic, and neuropathic pain
are difficult to manage. Personal fac-
tors associated with uncontrolled pain
are delirium, depression, anxiety, and
substance abuse.6
Psychological fac-
tors that modulate pain experience are
rarely initiators of pain in a cancer
patient. Depression is associated with
advanced disease and uncontrolled
pain.7
Since advanced cancer patients
experience a high prevalence and
severity of nonpain symptoms, pain
management must be combined with
systematic symptom control embed-
ded in the framework of palliative
care.8
137American Journal of Hospice & Palliative Medicine
Volume 21, Number 2, March/April 2004
Epidemiologyofcancerpainandfactors
influencing poor pain control
Mellar P. Davis, MP, MD, FCCP
Declan Walsh, MSc, FACP, FRCP (Edin)
MellarP.Davis,MP,MD,FCCP,DirectorofResearch,
The Harry R. Horvitz Center for Palliative Medicine,
ClevelandClinicFoundation,Cleveland,Ohio.
Declan Walsh, MSc, FACP, FRCP (Edin),
Medical Director, Director, The Harry R. Horvitz
Center for Palliative Medicine, Cleveland Clinic
Foundation, Cleveland, Ohio.
Palliative oncology update
at Universidad Nacional Aut Mexic on February 7, 2016ajh.sagepub.comDownloaded from

Epidemiology
Cancer causes 20 percent of all
deaths each year in the US, with
approximately one million new cases
per year. Of these patients, 500,000 or
more die as a result of their cancer.
Seventy percent of patients with
advanced cancer experience moderate
to severe pain. Many of these patients
have chronic pain as a result of past
treatment for their underlying disease.9
The incidence of cancer worldwide is
six to seven million patients per year,
with half or more occurring in develop-
ing countries.9,10
Every year, approx-
imately 4½ million patients die from
cancer, and 3½ million suffer from can-
cer pain daily. Only a fraction of those
will receive adequate pain treatment.10
Cancer incidence increases with
age. By the year 2015, the population
in developing countries will increase
by 60 percent, but the number of peo-
ple over 65 will more than double.
Therefore, despite a stable cancer
incidence, the absolute number of
cancer patients will also double. The
westernization of many developing
countries, particularly with regard to
tobacco consumption, will further
increase the incidence of cancer.11
Only 3 percent of the gross national
product of the average developing coun-
try is spent on healthcare.12
Global
resources for cancer control are finan-
cially limited. Therapies for advanced
cancer are expensive, technologically
involved, limited in benefit, and usually
beyond the means of developing
countries. Palliative medicine, though
often relegated to secondary impor-
tance in healthcare expenditures, is
much more important and affordable
in most countries.12
Pain characteristics
in advanced cancer
Patients with advanced cancer have
an increased frequency and intensity of
pain compared with early-stage cancer
patients. During treatment for their
cancer, 35 to 56 percent will have pain,
with 20 to 34 percent experiencing
severe pain. Pain type by percentage
includes: 1) somatic nociceptive pain
(50 percent); 2) neuropathic pain (33
percent); and 3) visceral nociceptive
pain (20 percent), with a median num-
ber of three types of pain per patient.
Six to 17 percent of patients with
nonmetastatic cancer have pain directly
attributable to cancer compared to 35 to
56 percent of those with metastatic dis-
ease. Pain is found in 76 percent of hos-
pice patients,13
and 84 percent require
opioids on the last day of life.14
Twenty
to 34 percent of patients have severe
pain, which directly influences their
quality of life and daily function (i.e.,
pain interference). Early-stage lung
cancer, breast cancer, cervical cancer,
and ovarian cancer rarely produce pain.
Prostate cancer and colon cancer pro-
duce pain even in the early stages by
obstruction of the urinary tract or fecal
stream, respectively.15,16
Solid tumors
produce more pain than leukemias and
lymphomas. Induction therapies for
acute leukemia are associated with pain
in 40 to 50 percent of patients on days
16 through 20 due to mucositis from
chemotherapy17
and neutropenia.
Grond et al.18
investigated cancer
pain etiologies and used a verbal catego-
ry rating scale to separate pain into cate-
gories: 1) pain related to cancer metas-
tases; 2) pain related to cancer treatment;
3) pain associated with complications
from cancer or its treatment (debility,
herpes zoster, etc.); and 4) pain unrelated
to cancer, treatment, or complications.
Pain was found most frequently in pa-
tients with advanced head and neck can-
cers, gastrointestinal malignancies, and
genitourinary tumors. Seventy-seven
percent of patients with pain had a verbal
rating of severe pain. Somatic nocicep-
tive pain was most frequently found
with breast cancer, genitourinary
tumors, bone primaries, and lym-
phoreticular malignancies. In compar-
ison, head and neck cancers produced a
mix of nociceptive and neuropathic pain.
Not surprisingly, gastrointestinal cancers
were associated with visceral nocicep-
tive pain. Nearly 40 percent of patients
had two pain syndromes, and 30 percent
had three or more separate pain syn-
dromes. Eighty percent of patients had
more than one anatomical site of pain.
The distribution of pain was nociceptive
in 50 percent of patients, usually due to
bone metastases. Twenty-five to 33 per-
cent of patients had neuropathic pain,
and a smaller subset had visceral pain.
Ten to 20 percent of patients had pain
caused by therapy rather than the under-
lying malignancies. Fewer than 10 per-
cent of patients had pain unrelated to
their cancer.
A survey by Twycross19
found one-
third of patients with bone pain, one-
third with neuropathic pain, and one-
third with pain caused by soft tissue
infiltration. One-third of patients also
had visceral pain, and 11 percent had
muscle spasms. In a second study by
Twycross,20
the median number of dis-
tinct pains was approximately three, and
40 percent of patients had more than four
separate pains. After four weeks of pal-
liative treatment, 78 percent of patients
still had more than one type of pain,
although the median number decreased
to 1.5. By numerical scale, there was a
graded influence of pain severity with
pain interference. When the pain in-
tensity rating exceeded 4 out of a possi-
ble score of 10, daily activities were
impaired. When pain intensity ex-
ceeded 6, significant interference with
enjoyment of life occurred.20
Pain in palliative outpatients.
Painwaspresentin61percentofpatients
attending a palliative day care clinic.21
The number of nonpain symptoms expe-
rienced in addition to pain range from
two to 11. Metastatic disease correlat-
ed with the number of symptoms and
the severity of pain. Associated non-
pain symptoms included nausea, dysp-
nea, insomnia, xerostoma, constipation,
irritability, sadness or depression, and
dizziness. One-quarter of patients had
138 American Journal of Hospice & Palliative Medicine

severe to very severe pain as observed in
a number of studies.12,22-26
Pain in pediatric patients. Child-
ren can complete a modified Memorial
Symptom Assessment Scale (MSAS)
adapted for children. As rated by the
MSAS, pain occurred in more than 35
percent and was associated with a high
degree of distress.27
Half of pediatric
patients admitted to an inpatient unit had
pain, and one-quarter of outpatients
experienced pain.28
Treatment-related
pain is more common than cancer-
related pain in adults. Pain related to
procedures (bone marrow, spinal taps)
and pain associated with surgery or
chemotherapy were the predominant
factors influencing pain prevalence.
Tumors cause pain in one-third of inpa-
tients and 20 percent of outpatients.
Tumor-related pain was mainly caused
by bony invasion, which is similar to the
findings for adults. Physicians tended to
underevaluate and underestimate pain
severity in children, as reflected in the
patient self-assessment visual analog
scales or face scales.
Breakthrough pain
Breakthrough pain (a transitory flare
of an underlying chronic pain) occurs in
most patients, and its incidence corre-
lates with pain severity.29,30
Break-
through pain has been described as inci-
dent pain (pain related to movement),
nonincident breakthrough pain, or end-
of-dose failure pain. Incident pain relat-
ed to bone metastases is the most com-
mon cause of breakthrough pain.
Sudden paroxysmal pain is a type of
neuropathic pain, usually caused by
compression or infiltration of peripheral
nerves or spinal nerve roots. Episodic
cramping abdominal pain is associated
with obstruction of a hollow viscus.
About 50 to 90 percent of patients
with chronic pain have breakthrough
pain. The severity of breakthrough pain
may be independent of the chronic
underlying pain, particularly incident
pain, and frequently requires dosing
independent of the around-the-clock
analgesic dose for chronic pain.
Breakthrough pain requires indepen-
dent assessment. The underlying can-
cer causes 76 percent of breakthrough
pain, while 20 percent is related to
treatment. The median pain duration
is approximately 30 minutes. Most
breakthrough pain is similar in charac-
ter to the chronic underlying pain.
Precipitating factors are found in 50
percent of the pain. Approximately
one-third of breakthrough pain is
somatic, 27 percent is neuropathic,
and 20 percent is a mixture of neuro-
pathic and nociceptive pain.29-32
Epidemiology of failed
pain management
Despite available universal guide-
lines, most studies demonstrate a fail-
ure to relieve pain in 38 to 74 percent
of cancer patients.12,33,34
Palliative
units that adopt the WHO stepladder
analgesic guidelines successfully
manage pain in 90 percent of
patients.35-37
The failed quality of care
in advanced cancer pain management
is usually described in terms of one or
two elements, though most failures
are the result of multiple factors. The
following are process barriers to pain
management:
• structural model of “disease”;
• failure to assess pain;
• lack of knowledge of opioid
pharmacology, conversion, equi-
analgesia, and rotation;
• failure to use adjuvants;
• failure to treat side effects;
• fear of opioid side effects, anal-
gesic tolerance, and addiction;
• lack of priority given to symp-
tom management;
• analgesia based on prognosis
rather than severity of pain;
• failure to document drug, dose,
timing, breakthrough pain, and
laxatives; and
• failure to follow up.
As described by deWit and col-
leagues,38
a Donabedian structure,
process, and outcome model for health-
care delivery can be used to evaluate the
shortcomings with pain therapy.39
The
Donabedian structure includes morphine
availability both nationally and interna-
tionally, arrangements for procurement
ofmorphine,proceduralmanuals,guide-
lines, assessment tools, patient educa-
tion, and educational materials for
healthcare providers. The Donadebian
process describes the practice of
guidelines within the patient-physician
relationship. The process includes actual
pain treatment practice with assessment
tools, dose adjustments, opioid switch,
the addition of adjuvants, continuity of
care, the use of patient education tools,
provisions to improve patient knowl-
edgeabouttreatments,andtheconsistent
practice of established guidelines. The
Donabedian outcomes are assessment of
response, quality of life, and patient sat-
isfaction with treatment. The failure of
pain management in developing coun-
tries occurs mainly within the structural
component of the Donabedian model. In
developed countries, failure most fre-
quently occurs within process of care.
International treaties began in 1912
with the Opium Convention, which was
created to minimize opioid abuse and
prevent the illegal trade of opioids.
These treaties required governments to
ensure the availability of opioids for
medicinal purposes. The International
Opium Conventions of 1925 set up a
permanent Central Opium Board that
monitored production and consumption
of opioids internationally. Until then,
most opioid abuse resulted from diver-
sion of legitimate sources.

The Single Narcotic Convention in
1961 established an International Nar-
cotic Central Board, which monitored
importsandexportsofopium.Incooper-
ation with national governments, the
board monitored opioid traffic to detect
diversion. This board was also estab-
lished to prevent a shortage of opioids
for legitimate purposes. In the United
States, the Drug Enforcement Agency
(DEA) was established to register
importers, manufacturers, and practi-
tioners who handled opioids. The focus
of these international treaties has been to
prevent abuse, but they have failed to
promote the legitimate use of opioids.
The illicit diversion from legitimate
sources of opium has become rare as a
result of these treaties.40,41
The unintended victim of the war
against illicit drug use is the cancer
patient. Increased regulation leads
directly to underprescribing and reduced
per capita consumption of morphine
nationally and internationally, but does
not alter illicit drug use. The increase in
regulations suggests to the public that
opioids are dangerous substances to be
avoided, and it implies that addiction to
opioids is common. The definitions of
addiction at the federal level are not per-
fect, but it is clear that cancer patients do
not fit the definition. However, at the
state level, the definition of addiction by
the state medical boards frequently fails
to separate psychological dependence
(addiction) from analgesic tolerance and
physical dependence.42
Morphine ad-
dictionissometimesdefinedas“habitual
use,” even though the pain management
guidelines encourage most patients with
chronic cancer pain to use morphine
habitually.42
In addition to the confus-
ing and misleading definitions of addic-
tion, another factor affecting opioid use
is the failure of most state medical
boards to promote the appropriate use
of opioids. Unlike federal authorities,
state law does not necessarily assure
opioid availability, and it can limit the
amounts prescribed. Some states require
prescriptions in triplicate, which can
reduce appropriate morphine use by
50 percent.41-46
Problems of pain management
in developing countries
India uses the same amount of mor-
phine as Denmark, even though
Denmark has 900 million fewer peo-
ple. India is a poor country and spends
six percent of its gross national prod-
uct on healthcare. Antibiotic acquisi-
tion and vaccines are given high prior-
ity, while pain management and
palliative medicine are of secondary
importance.47
Geographically, 75 per-
cent of India’s population is rural and
most pain centers are located in urban
areas. Patients are required to travel fre-
quently to urban pain centers to renew
their pain medications. Since there are
24 different languages spoken in India
and one-third of the males and two-
thirds of the females are illiterate, prop-
er pain assessment and pain diaries are
difficult to complete.47
Latin American countries face a
number of different problems. In
Argentina, the education of physicians
in the field of opioid pharmacology is
below par and often sporadic.48
Commercial opioids are expensive
and acquisition strains the limited
budget of the average citizen. There is
no overarching policy concerning pal-
liative care, nor are there adequate
insurance provisions for palliative
medicine and long-term domiciliary
care. In Columbia, the national supply
of opioids is inadequate and the anti-
quated law fails to recognize the benefits
of opioids in cancer pain management.49
In addition, the duration of opioid pre-
scriptions is limited. The war on drugs
has significantly hampered opioid avail-
ability. The average parenteral dose of
morphine in South American coun-
tries is approximately 9 mg/d com-
pared with 44 mg/d in the US.48-50
Opioid phobia is common in China,
particularly in areas affected by the
heroin traffic ranging from Laos to
Vietnam and into southern China.
Morphine is believed to be more
addicting than pethidine (meperidine).
Methadone is used only for addiction
therapy. Other barriers to appropriate
opioid use include inadequate assess-
ment, excessive regulations, inade-
quate physician knowledge of pain
assessment, and limited access to
potent opioids.51
Problems of pain management
in developed countries
Israel, where opioids are readily
available, also faces problems with pain
management.52
Healthcare workers have
inadequate knowledge of opioids and a
reluctance to prescribe morphine due to
the fear of addiction. Ninety percent of
physicians inadequately assess pain, and
training in pain management is also
inadequate.52
Most physicians are not
able to convert doses between various
opioids, nor can they calculate the
conversion of oral to parenteral equiv-
alents. Twenty percent of nurses are
reluctant to adequately medicate
patients.52
Patients under-report pain
and are reluctant to take pain medica-
tions out of fear of tolerance and
addiction.
In Canada, 67 percent of physicians
felt their education in pain manage-
ment was fair to poor.53,54
Fifty per-
cent of physicians do not use WHO
step three opioids as initial therapy for
severe cancer pain; and inadequately
titrate opioids. Assessment of patients
is also inadequate. Some patients are
reluctanttoreportpainortotakeopioids.
In Germany, even when an appro-
priate opioid is prescribed, 20 percent
of pharmacists counsel patients
against taking them, and one-third of
general community physicians dis-
continue the medication once the
patient returns to their care, because of
their own prejudice—not because the
therapy was ineffective.55
In the United States, opioids are read-
ily available and pain management

guidelines are well established. How-
ever, among oncologists of the Eastern
Cooperative Oncology Group, manage-
ment of cancer pain was felt to be less
than optimal in 80 percent of patients.56
Poor pain assessment occurs in 75 per-
cent of patients. Sixty-five percent of
physicians express concerns about side
effects, and most admit to being poorly
trained in pain management. Thirty per-
cent of physicians prescribe opioids
based on prognosis rather than pain
severity.56
Fewer than half of patients
within the hospital have recorded pain
assessments.57
Some professionals be-
lieve there is a ceiling to step three opi-
oids. There is underuse of adjuvant
coanalgesics and a general ignorance
of equianalgesic dosing.
Nearly 40 percent of nurses are
reluctant to give an adequate dose of
pain medications. Characteristically,
physicians undertreat by dose and nurses
undertreat by extending intervals be-
tween doses. Only 42 to 51 percent of
patients within a cancer center receive
adequate analgesics. Thirty percent of
those patients experiencing pain are not
treated. Almost two-thirds of patients are
reluctant to take pain medications out of
fear of tolerance, addiction, or side
effects. Curiously, there is poor correla-
tion between physician knowledge of
opioid pharmacology and a physician’s
prescribinghabits.Acultureofpoorpain
management tends to be self-propagat-
ing, and accountability for poorly con-
trolled pain was rarely reinforced until
recently.Apatientislesslikelytoreceive
adequate analgesia if elderly, female, a
member of a minority group, or within a
lower socioeconomic group.58,59
Summary
Pain is one of the most commonly
experienced and feared symptoms of
advanced cancer. Most cancer patients
experience pain, usually of moderate to
severe intensity, and most also have a
number of distinct types of pain.
Thefailuretomanagepainproperlyis
due to several factors. In developing
countries, it is likely to be related to
geography and limited resources. Legal
restrictions also present barriers. In
developed countries, it is usually related
to a “disease” rather than a “symptom”
model of care, which minimizes symp-
tom management. Other factors include
lackofphysicianeducationandfailureto
follow existing guidelines.59,60
Patients
fear addiction, drug tolerance, and side
effects.
Despite adequate resources, pain is
still undertreated. The WHO recog-
nizes the importance of pain manage-
ment as part of routine cancer care.
The establishment of effective pain
management requires comprehensive
assessment, competency with anal-
gesics, and communication with patients
and families.61
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