|Mark J. Lema, MD,
Professor and Chair
Department of Anesthesiology
State University of New York at Buffalo
R. Day, MD
Department of Anesthesiology
Texas Tech University
P. Myers, MD
Clinical Assistant Professor of Anesthesiology
State University of New York at Buffalo
A. Filadora II, MD
Clincal Fellow in Anaesthesia
Harvard Medical School
T. Plata, DC, MD
Advances in cancer treatment continue to lengthen survival
among cancer patients. As patients live longer, the need
for effective pain control has gained increased importance
for improving the quality of life. Patients with advanced
cancer often have pain as their chief complaint. The incidence
of pain varies, depending on the type if neoplasm, stage,
and the extent of spread. Because pain is a common symptom
in cancer patients, next to incurability, it is the most
With the current therapeutic modalities available to the
clinician, about 80% to 90% of cancer pain can be controlled.
However, studies by Cleeland, using Eastern Cooperative
Oncology Group (ECOG) physicians, show that most cancer
pain is under-treated, especially in regard to women,
minorities, and the elderly. Major barriers to effective
cancer pain control include:
Inadequate assessment by practitioners.
Under-reporting by patients and families.
Lack of knowledge regarding current treatment by practitioners.
Lack of accountability for effectively treating pain.
Fear if over-regulation by government officials.
Inadequate reimbursement or excessive paperwork by payers
for treatment of pain by
health care providers.
In an attempt to rectify the problems, the World Health
Organization (WHO), the American Society of Anesthesiologists,
and the Agency for Health Care Policy and Research (AHCPR)
have developed guidelines for the treatment of cancer
There are essentially five different causes of pain in
Acute cancer-related pain.
Chronic cancer-related pain.
Pain unrelated to cancer.
Chronic nonmalignant pain in opioid-tolerant patients.
Cancer pain is classified according to pain duration and
pain quality. Pain duration denotes the degree of chronicity.
The three temporal conditions are acute pain, chronic
pain, and incidental pain. Pathophysiological components
somatic (nociceptive) pain,
central pain, and
Breakthrough pain is a clinical term describing the episodic
exacerbations of pain above the established baseline,
which is experienced in up to 93% of cancer patients.
Doses of morphine, oxycodone, or hydromorphone, for example,
are given every 2 to 4 hours, as needed, to combat breakthrough
pain while the patient continues taking a long-acting
oral opioid agent. If a patient routinely uses breakthrough
medications, the daily total amount should be converted
to a sustained-release dosage and added to the current
Cancer Pain Syndromes
Although clinicians classify pain according to its onset,
duration, and nature, cancer pain is often experienced
as several different types of pain, with combined somatic
and neuropathic types the most frequent. During the course
of the disease, the pain changes as a result of tumor
progression or regression after treatment. These changes
may occur rapidly and illustrate the dynamic nature of
Pain is often the presenting symptom of a patient with
cancer. If it occurs early in the disease, patients may
endure high levels of pain in the expectation that adequate
anticancer therapy will relieve their symptoms. If it
occurs late in the course, pain often signifies disease
recurrence, which is associated with anxiety, apprehension,
Pain is also associated with diagnostic procedures such
as lumbar puncture or bone marrow biopsy, for example.
In addition, postoperative pain can persist after surgery
for tumor recurrence and may be complicated in patients
who are tolerant of opioids.
Anticancer therapy is frequently associated with painful
sequelae such as skin burns, mucositis, pharyngitis, and
cystitis after radiation therapy. Similarly, while receiving
drug chemotherapy, some patients experience myalgias,
gastrointestinal distention, or local irritation, for
example. Acute pain caused by the treatment occasionally
progresses to chronic pain. Usually, acute pain is self-limiting
and is most effectively treated with opioid analgesics
and nonsteroidal anti-inflammatory drugs (NSAIDs).
Chronic Pain Related to Cancer
Chronic pain related to cancer can be considered according
to the following categories:
Radiation Therapy-induced Pain
Pain After Thoracotomy
After thoracotomy, pain develops in the distribution of
the intercostal nerves in a small number or patients as
a result of partial or complete injury from retractors,
sutures, wires, or transaction. Pain usually develops
1 to 2 months after the operation and is described as
constant in the area of sensory loss, with occasional
Pain After Mastectomy
Patients who have has a radical mastectomy may experience
pain in the posterior part of the arm, axilla, and anterior
chest wall as a result of damage to the intercostobrachial
nerve. Pain typically develops 1 to 2 months after the
operation and is tight, constricting, and burning in mature.
Patients will tend to keep the arm in a flexed position
close to the chest wall, because movement exacerbates
the pain. As a result, a frozen shoulder may develop from
reduced joint motion. Reports of phantom breast pain occasionally
appear in the literature.
Pain After Radical Neck Dissection
Pain can arise as a result of surgical intervention, including
radical neck dissection. This pain is characterized as
being constant, with dysesthesia and shock-like sensation
as a result of interruption of the cervical plexus nerves
and peripheral nerves serving those areas.]
Phantom Limb Pain
Phantom limb pain occurs in a large number of patients
after amputation and usually produces a burning and cramping
sensation in the area of the original limb. It can easily
be differentiated from stump pain, which occurs at the
site of the amputation and is elicited by palpation or
percussion of the stump area.
Pain Unrelated To Cancer
Approximately 3% of the pain syndromes that occur in cancer
patients have no relation to the underlying cancer or
cancer treatment] Most commonly, pain is caused by degenerative
disk disease, arthritis, fibromyalgia, or migraine and
has often predated the diagnosis of cancer. In these patients,
pain does not necessarily signify recurrent disease; however,
a chronic illness behavior has already developed in many
patients. Careful assessment and early psychological intervention
And Opioid-Tolerant Patients
Opioid-tolerant pain patients a challenging group. These
patients may have used opioids illicitly in the past,
but are no longer using them. Many are reluctant to take
opioids for their cancer pain, fearing an addiction potential.
These patients require support and understanding of the
necessity to treat the pain. The liberal use of adjuvant
therapies allowing for decreased opioid does is also beneficial.
Cancer pain that develops in patients who have been taking
opioids for other medical conditions requires higher doses
of opioids] In these cases, the use of adjuvants and early
intervention with block techniques or the use of more
potent opioid receptor agonists may avoid dose escalation
without good pain control] Patients who use more than
50 mg of oral morphine for longer than 3 months often
require three times more drug for a three-times-longer
duration than opioid-naive patients after surgery]
Assessment Of Cancer Pain
Assessment of cancer pain begins with a thorough understanding
of the complex nature of pain. The International Association
for the Study of Pain defined pain in 1979 as "an
unpleasant sensory and emotional experience associated
with actual or potential tissue damage or described in
terms of such damage." This definition stresses the
importance of the emotional and suffering aspects of pain.
Treatment failure can often be directly attributed to
an inadequate assessment by the physician of the patient
with cancer pain. Initial treatment should be based on
the cause and type of pain. Prior to beginning treatment,
the clinician should perform a detailed history and physical
examination. Based on the findings of the examination,
diagnostic studies should be ordered; a preliminary diagnosis,
treatment goals, and a treatment plan are then established.
Following the initial evaluation, on subsequent visits,
the patient's status should be reassessed, as tumor growth
is a dynamic and evolving process.
And Physical Examination
To determine what further testing a patient may require,
the location, quality, and duration of the patient's pain
should be elicited. A complete review of the past medical
history and what, if any, therapeutic measures have been
previously tried to relieve pain may provide valuable
information for developing a treatment plan. Physical
examination should include a complete neurological examination.
Neurological deficits from direct tumor invasion or compression
are common and are frequently painful.
In addition to pain, most patients with cancer have numerous
other symptoms. They often suffer from insomnia, depression,
fatigue, and the side effects from therapeutic intervention
such as headache and nausea, for example. One should take
into account all the symptoms and develop a therapeutic
plan that will improve quality of life for the patient.
One of the most difficult aspects of pain control is the
accurate assessment of pain intensity. Although intensity
is difficult to gauge, it is important because it provides
a basis for developing a treatment plan and evaluating
the effectiveness of therapeutic interventions. Also,
if a patient's pain level increases during treatment,
it may indicate disease progression. The best methods
for determining pain intensity are the Verbal Scale or
the Visual Analogue Pain Scale (VAPS) and the McGill Pain
Following a thorough review of the patient's medical condition,
a preliminary treatment plan should be established. Functional
status and quality-of-life issues are also critically
important to assess. Provisions for supportive care should
be discussed and the emotional stress on family members
as well as the psychological well being of the patient
should be considered.
After a treatment plan has been established, the patient's
expectations in terms of pain control should be discussed.
Often patient's have unrealistic goals and may not understand
the extent of the disease. If necessary, the help of the
primary care physician can be obtained to communicate
with the patient.
Oral And Parenteral Analgesia
Pharmacotherapy is the most widely used method of pain
control. Three categories of analgesic medications are
commonly available: NSAIDs, opioid analgesics, and adjuvant
Nonsteroidal Anti-Inflammatrory Drugs
The peripheral effects of NSAIDs inhibit the enzyme cyclooxygenase,
decreasing tissue levels of prostaglandins, which are
the inflammatory mediators that sensitize peripheral nociceptors
in the skin. NSAIDS have an anti-inflammatory action and
an inhibitory effect on bone tumor growth by the inhibition
of prostaglandin E2 release. They may also have a centrally
medicated analgesic effect.
Acetaminophen has an analgesic effect by inhibiting nitric
oxide synthetase, an action that is centrally and spinally
mediated and similar in efficacy to that of aspirin. Also,
NSAIDs possess a therapeutic ceiling dose, above which
further dose increments provide little relief. Toxicity,
however, increases and includes nausea, gastritis, and
Opioid analgesics are the mainstay of therapy for cancer
pain. The objective is to control pain while minimizing
distressing side effects. The success of this therapy
depends on the expertise of the prescriber, who must know
the nuances of pharmacological features among various
opioids and must be experienced in their use to make an
appropriate selection for each patient.
Patients who don't respond to second-step opioids are
switched to opioids on the third step of the ladder, most
often morphine, hydromorphine, oxycodone, or fentanyl.
Morphine has been used extensively worldwide and has been
endorsed by the WHO. It is also available in several formulations
and lends itself to administration by different routes.
When a physician selects a route for administration, factors
such as gastrointestinal upset or obstruction, outpatient
versus inpatient setting, and patient compliance should
be addressed. Oral administration is the preferred and
most economical route, although some medications may be
given rectally when doses by both routes are considered
A widely accepted principle of effective management of
cancer pain with opioids is dosage administration at fixed
intervals on an around-the-clock basis. This approach
provides sustained analgesia and avoids the peak and trough
effects of medication given as needed. When sustained-release
agents are used, additional opioids should also be available
for breakthrough pain at all times during the course of
treatment. Doses must be titrated to the patient's need,
thereby avoiding side effects from overdosing or persistent
pain from inadequate analgesia.
Adjuvant medications are used in conjunction with oral
or parenteral analgesics. They
have inherent analgesic action, improve mood or sleep,
or alleviate nausea,
and somnolence. The tricyclic antidepressants are known
to have analgesic action.
They alleviate depression, improve sleep, and benefit
patients with neuropathic
Anticonvulsive drugs and the antispasmodic baclofen are
helpful in patients with
Mexiletine has been used in neuropathic pain from cancer
after its success in the
treatment of painful diabetic neuropathy.
Corticosteriods are useful adjuvants and have been shown
to improve analgesia,
mood, and appetite in the short term.
The transdermal therapeutic system with fentanyl (patch)
has simplified the concept of continuos parenteral administration
of opioid by using a noninvasive method. This method has
been beneficial in the treatment of cancer pain with high
patient preference. Fentanyl is the sole opioid available
by this method because of its high lipid solubility.
After initial application of the patch, serum levels gradually
increase to peak concentration in 12 to 24 hours, and
effective analgesia occurs as early as 6 hours. The patches
are marketed in dosages of 25, 50, 75, and 100 mg/hr and
are applied for 72 hours. Because these dosages are additive,
a patient requiring 150 mg/hr of transdermal fentanyl
may have two 75-mg/hr patches.
Patient-controlled analgesia (PCA) allows patients to
treat their own pain by self-administering prescribed
doses of opioids parenterally by means of a small, sophisticated
programmable, computerized pump. The pump can be programmed
to deliver a continuous infusion; in addition, the patient
can administer bolus injections at a preset dose and time
interval. There appears to be no difference in the effects
on respiratory function compared with other therapies.
With the development of the multidisciplinary approach
to pain management and with an increasing range of available
pharmcological agents, fewer patients require surgical
intervention. The aim of surgery is to interrupt the nociceptive
pathways in the peripheral nerves or at certain sites
in the neuraxis.
The most common performed surgical procedure for cancer
pain relief is anterolateral cordotomy, which targets
the spinothalamic tract. This can be done by open technique,
which carries significant morbidity; complications include
hemiparesis, urinary retention, and sexual impotence.
Percutaneous cordotomy has largely replaced the open method.
It is usually performed with the patient under local anesthesia
by advancement of a thermal coagulation probe with fluroscopic
guidance. It is ineffective for those with neuropathic
pain caused by a central mechanism and has only limited
use for visceral pain.
Intraspinal administration of opioids is frequently used
in the treatment of pain, especially pain that in not
controlled with oral medications. Opioids can be delivered
by the spinal or epidural route. Advantages include profound
analgesia, often at a much lower opioid dose without the
motor, sensory, or sympathetic block associated with intraspinal
local anesthetic administration. The opioid dosage is
usually much lower; approximately 20% to 40% of the systemic
dose is given epidurally, and only 10% of the epidural
dose is used if given intrathecally, thereby lowering
the risk of side effects. Placement of an intrathecal
pump initially is a much more complex and costly procedure
in comparison to epidural catheter placement. However,
the high cost of implantation may be negated by the sustained
home maintenance costs of epidural infusion after 4 to
Three systems used for chronic intraspinal opioid administration
Percutaneous tunneled epidural catheters
Tunneled epidural or spinal catheters connected to subcutaneously
Patients suffering from cancer pain localized in a certain
area of the body, which manifests as peripheral neuralgia
or visceral pain, are excellent candidates for regional
block with neurolytic agents. These techniques are also
appropriate in patients who are extremely ill or debilitated.
Implanted spinal infusion pump systems
The management of patients with cancer pain can be a challenging
task, even for physicians trained in cancer pain management.
The use of a systemic approach in assessing such pain
can simplify management. Without a thorough assessment,
the possibility of misdiagnosis and undertreatment exists.
Appropriate and frequently times assessments form the
basis for the development of an effective pain treatment
plan. An understanding of the various etiological mechanisms
of cancer and the different types of pain that they can
produce is essential to providing appropriate therapeutic
interventions. Finally, a multidisciplinary approach addressing
pain, anger, anxiety, depression, and associated symptoms
is essential in providing the best quality of life during
this life-threatening experience.
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