Why Cancer Pain?

For the more than 10 million people worldwide who are diagnosed with some form of cancer
each year, pain associated with their condition is a serious concern. Although pain is not
necessarily inevitable for everyone with cancer, it is common. Approximately one-third of adults
who are actively receiving treatment for cancer and two-thirds of those with advanced malignant
disease experience pain. Children with cancer have similar pain experiences. While increasing
numbers of medical professionals and governments are beginning to place more attention on the
pain suffered by long-term survivors of cancer, much more research is needed.

The consequences of unrelieved cancer pain are devastating and can include functional
impairment, immobility, social isolation, and emotional and spiritual distress. In some cases,
cancer pain that is not managed can lead to the cessation of potentially curative therapies,
ultimately having a negative impact on the patient’s survival. Cancer patients express greater fear
of dying in pain (i.e., suffering) than dying. Family and friends also suffer as they witness the
pain and anguish experienced by a loved one with cancer.

Every country, community, and family in the world is affected by cancer and its related pain.
Focusing on a central theme of “Raising Awareness ▪ Improving Treatment ▪ Growing Support,”
this yearlong campaign aims to foster greater understanding of the serious pain cancer patients
often confront and, ultimately, provide more effective and accessible treatment options to
minimize pain and suffering.

Cancer Pain Issues

Barriers to effective pain treatment

Although many types of cancer can be diagnosed and treated early, and more patients are being
cured every year, statistics show that far too many cancer patients experience cancer-related
pain. There are several reasons behind this problem. Most notably, patients are often denied
sufficient pain medication due to opiophobia (fear of opioids) among doctors, nurses, patients,
and family members. Governmental restrictions on pain medication, as well as patients’ financial
limitations, can also affect an individual’s access to effective pain medications, including
opioids.

In addition, as increasing numbers of cancer patients survive, a variety of treatment-related

chronic pain issues has surfaced, including:

 Post-surgery pain
 Chemotherapy-induced neuropathic pain
 Anti-estrogen therapy-related musculoskeletal pain
 Radiotherapy-induced pain

Factors affecting cancer pain

For many patients around the world, cancer remains a terrifying disease that often produces
uncertainties and losses not only for the patient, but for his or her loved ones as well. We know
that several factors can directly impact the ability to control a patient’s pain, such as:

 Emotions, including anxiety and depression

 Cognition, such as a person’s confidence in his or her ability to cope with pain, pain
catastrophizing, and hopelessness
 Social context, including the support a patient receives from his or her partner or family

These factors, along with the physical, tissue, and nerve-injury-related components of pain, are
all core contributors to cancer pain. Once we gain a better understanding of the
neurophysiological basis of how psychosocial processes modulate pain, we will be better
positioned to treat and manage the pain more effectively. Moreover, this enhanced understanding
will enable us to identify psychosocial interventions that can further reduce the pain and
suffering associated with cancer pain.

Complementary therapies

Researchers are interested in how pain affects everyday life. And if complementary therapies
alongside cancer treatments can help to relieve pain.

In one study researchers are looking at how art therapy can change the experience of pain after
breast cancer treatment. They also want to see if and how art therapy sessions can affect people’s
experience of constant pain.

Another trial team are researching acupuncture. They want to find out if it can help people with
nerve damage symptoms, such as pain, caused by chemotherapy. Acupuncture uses fine sterile
needles. You have these needles put just under the skin at particular points on your body.

Doctors usually treat nerve damage with drugs to help with changed nerve sensations. These
drugs include gabapentin, amitryptlline, pregabalin and some creams and gels. These can help,
but doctors want to improve treatment for this group of people. In this trial, they are looking at
acupuncture alongside the usual treatments. (UK Research Cancer).

Definition

Cancer pain is a complex, temporally changing symptom which is the end result of mixed
mechanism pain. It involves inflammatory, neuropathic, ischemic, and compression mechanisms
at multiple sites.5 It is a subjective, heterogeneous experience that is modified by individual
genetics, past history, mood, expectation, and culture.

Cancer pain syndromes are categorized as acute and chronic based on onset and duration. Acute
pain syndromes have a sudden, well-defined onset, an identifiable cause (e.g. surgery), subject to
sympathetic output (fight or flight response), and are expected to improve with management.
Chronic pain on the other hand, has a less distinct onset, has a prolonged and fluctuating course,
and is largely driven by central sensitization and neuroplastic responses from acute injury.6,7 It is
often characterized by "pain flares" referred to as breakthrough pain.8

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Prevalence

Figure 1: Click to Enlarge

In 1986, the World Health Organization (WHO) developed a 3-step analgesic ladder (Figure 1)
to guide cancer pain management worldwide.9 A 10-year prospective, validation study of the
WHO analgesic ladder showed more than 70% of cancer patients achieved good pain relief using
WHO recommendations.4 However, more than 25 years later, cancer pain is still a major
problem. Prevalence is high in the range of 60 to 80% in advanced cancer patients. When
present, cancer pain is moderate in severity and interferes with activity and enjoyment of life to a
great extent.10

Patients with bone metastases are more likely to report severe pain than those with soft tissue
metastases.11,12 Despite the direct correlation of pain prevalence with stage of cancer, pain
corresponds poorly to the observed tumor burden and severe pain can occur in all cancer stages.13
Patients with cancer of the pancreas, bone, brain, lymphoma, lung, and head and neck have the
highest prevalence of pain.14 Most pain is the result of their underlying cancers (85%), secondary
to antineoplastic therapies (17%), and comorbidities unrelated to cancer (9%).15 Common causes
of pain16 are listed in Table 1.
Table 1. Common Causes of Pain in Cancer Patients

Malignancy-Related Antineoplastic therapies Other comorbidities

 bone metastases  side effects from  immobility
 soft tissue metastases chemotherapy,  constipation
 visceral metastases immunotherapy,  thrombophlebitis
 leptomeningeal hormonal therapy, and  unaddressed psychococial
metastases radiation therapy and psychiatric issues
 epidural spinal cord  post-procedural and post-
compression surgical pain
 malignant bowel
obstruction
 pathologic fracture
 hemorrhage into a
tumor
  tumor-related
neuropathic pain

Pathophysiology

Figure 2: Click to Enlarge

Cancer pain shares the same neurophysiologic pathway as non-cancer pain. This process of
nociception involves activation of the sensory afferents by persistent noxious stimuli,
transduction, transmission, modulation, and perception.17

Stimuli from tissue injury activate primary afferent neurons called nociceptors, found in skin,
muscle, joints, and some visceral organs. Nociceptors are high-threshold receptors that are silent
until significantly stimulated.18 Most nociceptors are polymodal, responding to thermal, physical,
and chemical stimuli. Neuron cell bodies are located within the superficial laminae of the dorsal
root ganglia and trigeminal ganglia. Once depolarized, transmission occurs proximally via thin
myelinated A-δ fibers (fast) or unmyelinated C fibers (slow). Interneurons within laminae I and
II of the dorsal horn amplify or dampen neurotransmission. Afferent axons terminate in lamina I
or II, and second-order afferent neurons cross the midline and ascend all the way to the
brainstem and thalamus in the anterolateral quadrant of the contralateral half of the spinal cord.
Together with axons from second-order lamina I neurons, these fibers form the spinothalamic
tract, the major ascending pathway for information about pain and temperature (Figure 2).
Sensory fibers associated with affective responses also ascend in the contralateral dorsolateral
spinal cord to the medial thalamus or brainstem and then to the cingulate cortex and limbic lobe.
Downward modulation occurs through the periaqueductal gray (PAG) and rostral ventral
medulla (RVM) with axons that transverse the dorsal lateral funiculus. These modulate pain
directly by connections to secondary afferent neurons in the dorsal horn or via connections with
interneurons in laminae I and II (Figure 2).19 The neurochemistry of these processes involve
multiple neurotransmitters including endorphins, prostraglandins, gamma-aminobutyric acid
(GABA), cannabinoids, and many others, that are targets for analgesic medications.17
Given the complexity of pain neurophysiologic and neurochemical processes, clinicians need to
integrate findings from history, physical examination, and tests in order to assess
pathophysiologic mechanisms and etiology. Inferred pathophysiologies (Table 2) are
nociceptive, neuropathic, or psychogenic. Disorders that cannot be categorized are idiopathic.
Cancer pain is oftentimes a mixed disorder.8
Table 2. Inferred Pathophysiologies of Cancer Pain

Table 2. Inferred Pathophysiologies of Cancer Pain

1. Nociceptive

a. Somatic (bones, joints, muscles)

b. Visceral (hollow viscus, organ capsules, myocardium)

2. Neuropathic
3. Psychogenic
4. Idiopathic

Nociceptive pain is from an acute or persistent injury to somatic or visceral tissues. Somatic
nociceptive pain is described by patients as "aching", "stabbing", or "throbbing" and involves
injury to bones, joints or muscles. Visceral nociceptive pain results from injury to viscera. It is
poorly localized and characterized as "cramping" or "gnawing" if it involves a hollow viscus
(e.g. bowel obstruction). It may be described as "aching", "stabbing", "sharp", similar to somatic
nociceptive pain, if it involves other visceral structures (e.g. organ capsules, myocardium).
Visceral pain is often referred to somatic sites due to convergence on somatic afferents within
the dorsal root ganglia and dorsal horn. Referral correlates with visceral pain severity.20

Neuropathic pain syndromes are varied and suggest injury to the peripheral or central nervous
system. It is often associated with referred pain (pain is perceived in a location that is not the
source of the pain), allodynia (pain induced by non-painful stimulus), hyperpathia (exaggerated
pain response to nociceptive stimuli), or dysesthesia (unpleasant, abnormal sensation in an area
of neurologic deficit). Pain courses in the distribution of motor, sensory, or autonomic nerves,
except when pain is funicular or central, causing burning or lancinating pain in an area of
decreased or absent sensation (e.g. in patients with spinal cord injuries).21

Psychogenic pain refers to pain predominantly sustained by psychological factors. Although

psychogenic pain is rare in the cancer population, psychosocial and psychiatric evaluations are
important in pain assessments. Psychosocial and psychiatric issues contribute to the pain
experience and may worsen pain and pain-related distress.17

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Signs and Symptoms

Acute pain syndromes (Table 3) are often iatrogenic (i.e. due to tests or treatments) but may also
be disease-related complications. Chronic pain syndromes (Table 4) are mostly due to direct
effects of malignancy and some are due to antineoplastic treatments.22 Acute pain is associated
with generalized sympathetic hyperactivity, resulting in diaphoresis, hypertension, and
tachycardia. Tolerance to sympathetic hyperactivity develops quickly as pain becomes chronic.
Overt pain behaviors such as grimacing, moaning, and splinting, as well as sympathetic
hyperactivity, are not present with chronic pain.23 Unrelieved chronic pain produces depression,
anxiety, anorexia, asthenia, and insomnia.
Table 3. Acute Pain Syndromes

Causes
Antineoplastic therapies (i.e.
chemotherapy, hormonal treatments,
immunotherapy, radiation therapy)
Procedures
Associated with disease
Disorders
Mucositis, neuropathies, enteritis, proctitis, cystitis,
arthralgia, myalgia, angina, diffuse bone pain, flare
syndrome, palmar-plantar erythrodysesthesia (hand-foot
syndrome)
Post lumbar puncture headache, post-biopsy pain, pain
due to therapeutic interventions (eg. paracentesis, chest
tube placement, stent placements, vascular embolizations)
Hemorrhage into a tumor, pathologic fracture, obstruction
or perforation of hollow viscus, venous thromboembolic
disease

Table 4. Chronic Pain Syndromes

Causes
Nociceptive somatic pain due
to bone metastases
Nociceptive somatic pain due Headache and facial pain, ear and eye pain, pleural pain, muscle
to soft tissue involvement
Nociceptive visceral pain due
to malignancy
Neuropathic pain due to
malignancy
Antineoplastic therapies (i.e.
chemotherapy, radiation
therapy, hormonal
treatments, surgery)
Disorders
Multifocal bone pain, vertebral pain syndrome in epidural spinal
cord compression, pain syndrome related to pelvis and hip, base of
skull
cramps
Hepatic distention syndrome, chronic bowel obstruction, midline
retroperitoneal syndrome, malignant perineal pain, ureteric
obstruction
Radiculopathies, mononeuropathies, plexopathies, neuralgias,
peripheral neuropathy
Peripheral neuropathy, chronic post-surgical pain (eg.mastectomy,
thoracotomy, neck dissection, pelvic surgeries), phantom limb
pain, chronic radiation myelopathy, chronic radiation plexopathy,
chronic radiation proctitis and enteritis, lymphedema pain,
osteoradionecrosis

Diagnosis

Accurate assessment is the first major step necessary for good pain management. Adequate
assessment requires a thorough pain history (Table 5) and physical examination before
radiographic studies or physiologic testing. Bypassing a good history and physical examination
for radiographs is misleading, since correspondence between the report of pain severity and
presence of underlying pathology is poor.24 Location, radiation, quality, intensity and temporal
pattern of pain, along with provocative and palliative factors associated with pain, map the pain
source and provide clues to a possible cause. The date of onset, associated symptoms, and pain
trajectory measures disease course and prognosis indirectly and crudely. Past trials of therapy,
including over-the-counter medications and home remedies, should be recorded. Crescendo or
altered pain patterns, in addition to the usual chronic pain, indicate cancer progression, treatment
or cancer complications, or cancer recurrence, until proven otherwise.
Table 5. Components of the Pain History

1. Location of pain
2. Onset
3. Provocative or Palliative factors
4. Quality
5. Radiation and Related symptoms
6. Severity (Intensity and effect on function)
7. Temporal Pattern

a. Continuous
b. Intermittent Pain
i. Incident (associated with a known precipitating event)
ii. Non-incident (Breakthrough, spontaneous)
iii. End-of dose failure (occurs just before a scheduled opioid dose)

Pain severity is assessed by unidimensional pain scales, such as the visual analogue, numerical,
or category scales.24 Pain-relief scales have the advantage of gauging patient-reported benefits to
treatment but do not correlate closely with unidimensional scales; they tend to be more optimistic
than unidimensional scales. Patients might have pain relief but still have severe pain that
interferes with activities of daily living (ADLs).25 Comprehensive multidimensional scales are
more burdensome for patients to complete, but they can evaluate the affective component of pain
and pain interference with activities. Several general quality-of-life scales include pain-intensity
or pain-relief scales. Examples are the QLQ-C30 of the European Organization for Research of
Cancer and the Functional Assessment of Cancer Therapy (FACT) Scale.26

Physical examination is centered to the area of pain but should not be misguided by referred
patterns of pains. For example, hepatic metastases refer pain to the shoulder. Anatomic
examination is followed by maneuvers to elicit or ameliorate pain. Bone metastases are common,
local palpation and manipulation elicit pain. Spinal cord compression from epidural tumor
extension is most feared by physicians. Hence, a neurologic examination, manual muscle testing,
percussion tenderness and joint mobility, and inspection for muscle symmetry are important
parts of the physical examination. Assessment of psychiatric and psychosocial comorbidities is
important to address factors that may adversely affect pain perception and worsen distress.17

Radiographic studies are guided by the history and physical examination, stage of disease,
patient performance status, therapeutic options, and goals of care. Terminally ill patients, or
those for whom little is gained by radiographic procedures, should be treated with palliative
measures and not be subjected to painful, unnecessary testing. If diagnostic imaging is
appropriate, pain is treated first so that patients are comfortable and able to complete their
procedure. Plain radiographs of painful areas are still valuable. Magnetic resonance imaging
(MRI) of the spine and brain and computed tomography (CT) scanning of the chest and abdomen
provide the greatest amount of information. Ultrasonography of pericardial effusions and biliary
and urinary tract obstructions is easily accomplished, portable, and without radiation exposure.
Electrophysiologic studies separate mononeuropathies or entrapment neuropathies from
plexopathies, and ulnar or peroneal entrapment syndromes from brachial and lumbar
plexopathies, respectively. Conduction velocities, specific latencies, amplitudes, duration, and
configurations of sensory and motor evoked potentials identify and locate neuropathology.
However, electrophysiologic studies are normal with significantly damaged nonmyelinated
fibers.

Treatment

Cancer pain is relieved in 80% to 90% of patients using an opioid-based analgesic regimen and
the WHO analgesic ladder (Figure 1) as guidelines.27,28 Opioids are preferably given orally, used
with around-the-clock (ATC) dosing, according to the analgesic ladder, with individualized
treatment based on pain patterns, and with attention to details.29 In countries where strong
opioids (Table 6) are readily available and where palliative care is established, Step 2 in the
analgesic ladder is bypassed and low doses of potent opioids are used instead.30

For many years, morphine, has been deemed the opioid of choice for moderate to severe cancer
pain. Recent recommendations31 have also endorsed the use of oxycodone and hydromorphone as
first line opioids for cancer pain. In treating continuous pain, use ATC normal-release opioid
such as immediate-release morphine, oxycodone or hydromorphone every 4 hours or sustained-
release morphine, oxycodone, or hydromorphone every 12 hours. Reasonable initial doses of
strong opioids are listed in Table 6.
Table 6. Strong Opioids and Initial Doses for Opioid Naïve Patients

Opioid Oral Formulation Parenteral Formulation

Dose (Immediate release) Interval Dose (Intravenous) Interval (prn dosing)
Morphine 5-10 mg 4 hours 0.5 - 1 mg 1 hour
Hydromorphone 2 mg 4 hours 0.2 mg 1 hour
Oxycodone 5 - 10 mg 4 hours N/A N/A
Fentanyl N/A N/A 25 mcg 1 hour
Methadone 5 mg (2.5mg in the elderly) 12 hours0.2 mg 1 hour

Rescue doses of normal-release opioids should be provided for intermittent pain. Intermittent or
breakthrough pain may be incident (i.e. related to movement or activity), non-incident
(spontaneous), or end-of-dose-failure.32 Recommendations for rescue dosing are 25% to 50% of
the 4 hourly dose, or the 4 hourly dose given hourly, or 10 to 20% of the total daily opioid dose.
End-of-dose failure is due to suboptimal doses of ATC opioids and is improved by titrating the
ATC opioid dose rather than shortening the dosing interval.32 Rescue doses need to be titrated to
response if the underlying chronic pain is under control.
Rescue doses of normal-release opioids should be provided for intermittent pain. Intermittent or
breakthrough pain may be incident (i.e. related to movement or activity), non-incident
(spontaneous), or end-of-dose-failure.32 Recommendations for rescue dosing are 25% to 50% of
the 4 hourly dose, or the 4 hourly dose given hourly, or 10 to 20% of the total daily opioid dose.
End-of-dose failure is due to suboptimal doses of ATC opioids and is improved by titrating the
ATC opioid dose rather than shortening the dosing interval.32 Rescue doses need to be titrated to
response if the underlying chronic pain is under control.

Individualized dosing needs to take into account age, perhaps gender, drug interactions, and
organ system dysfunction. Alternative opioids are chosen based on organ failure. Morphine and
hydromorphone are safe in mild to moderate hepatic impairment, dose reduction and/or
lengthening of dosing interval should be done in patients with severe hepatic impairment.
Methadone, fentanyl, and buprenorphine are relatively safe, with few dose adjustments necessary
for renal failure. Oxycodone pharmacokinetics is significantly altered by hepatic and renal
failure. Drug interactions should be noted as they are least with glucuronidated opioids like
morphine and hydromorphone and more problematic with opioids metabolized through the
CYP450 enzyme system (e.g. fentanyl, oxycodone, and methadone).33 Assess for dose-limiting
side effects (e.g. nausea, myoclonus, delirium, hallucinations, and respiratory depression), titrate
doses slowly or switch opioids if needed.

Some patients develop intolerable side effects before achieving pain relief. A retrospective
study34 showed that common reasons for opioid rotation were cognitive failure, hallucinations,
myoclonus, nausea and vomiting, local toxicity, and refractory pain. One strategy to obtain a
balance of analgesia and side effects is to switch or rotate opioids.32 Opioid rotation results in
resolution of side effects and improved pain control in >50% of patients.34 It is important to
consider patient and disease related factors, medical comorbidities, concomitant
pharmacotherapy, patient's history of any drug sensitivities, the clinical care setting (outpatient,
inpatient, long-term care, and hospice) and financial or insurance related issues when rotating to
an alternate opioid.35 Other options in managing patients who fail to achieve pain relief due to
dose-limiting side effects are as follows:32

 Reduce the systemic opioid dose by 25 to 50 % and simultaneously add a non-opioid or

adjuvant analgesic to maintain pain control
 Change the opioid route (i.e. parenteral or spinal route)
 Symptomatically manage opioid adverse effects (Table 7)
Table 7. Opioid side effects and management

Side Effects Interventions

 May use metoclopramide, or neuroleptics (eg. haloperidol, olanzapine)
Nausea and as needed.
vomiting  Common at the start of therapy and usually resolves in 7 to 10 days.

 Use stool softeners and laxatives.

Constipation  Prevention is key as no tolerance is developed to this side effect.
  Reassurance.
 Need to review medication list to rule out other medications potentially
causing sedation.
Sedation  Tolerance is developed days after starting opioid therapy.
 If persistent, consider reducing opioid dose and use a stimulant (e.g.
methylphenidate).

 Reduce dose of opioid and start haloperidol as needed.

 Review medication list to remove other drugs that may cause delirium
Confusion and rule out other potential causes (e.g. sepsis).
 Consider switching to a different opioid.

 Reduce dose of opioid and prescribe clonazepam as needed.

 Consider adding an adjuvant analgesic to optimize pain control and
Myoclonus
lessen intolerable side effects.

 Use ondansetron 8 mg IV x 1 dose or 8 mg PO BID for 3-5 days.

Pruritus

Common initial side effects of opioid therapy are mild nausea and vomiting, drowsiness,
lightheadedness, and sedation which usually resolve over several days.30 Nausea may require
antiemetics. Constipation is a common side effect that persists and is treated proactively with
stool softeners and laxatives. The most feared opioid side effect is respiratory depression, which
fortunately is uncommon.28,36 Strong opioids do not cause clinically important respiratory
depression in patients having pain.37 However, care must be taken in those who are frail, opioid-
naïve, or who have comorbid conditions that predispose to respiratory failure such as chronic
obstructive lung disease, or who are on sedative medications. Respiratory depression from
opioids is nearly always associated with sedation and miosis. Naloxone is given only if sedation
is accompanied by bradypnea and only in doses that reverse respiratory depression and not
analgesia. A 0.4 mg vial of naloxone is diluted in 10 mL of saline; a 1 mL aliquot is given every
1 minute and titrated to the level of consciousness. Patients on sustained-release opioids or
methadone require a continuous infusion of naloxone at the dose that reversed respiratory
depression, because the half-life of naloxone is only 30-90 minutes.
Table 8. Non-opioid Analgesics

Acetaminophen
NSAIDs

 Preferential Cox-1 Inhibitors (e.g. indomethacin, ketorolac)

 Non-selective COX inhibitors (e.g. aspirin, fenamates, ibuprofen, naproxen, salicylates)
 Preferential COX 2 inhibitors (e.g. celecoxib, diclofenac, etodolac, meloxicam,
nabumetone)
Management of cancer-related pain also requires expertise in the use of non-opioid analgesics
(Table 8), acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), and adjuvant
analgesics (Table 9). Acetaminophen is a centrally-acting non-opioid analgesic, used widely in
prescription and over-the-counter (OTC) medications to relieve mild to moderate pain and fever.
From 1998 to 2003, acetaminophen was the leading cause of acute liver failure in the United
States.38 Patients should be advised not to exceed the maximum total daily dose of 4 grams and
should be educated on the importance of reading all medication labels to ensure they are not
taking multiple acetaminophen containing products.38 Caution should be observed in patients
with severe hepatic impairment especially if associated with alcohol dependence and
malnutrition.
Table 9. Adjuvant Analgesics for Cancer Pain Treatment

Category Based
Drugs
on Clinical Use
Glucocorticoids, tricyclic antidepressants (TCA), serotonin-norepinephrine
Multi-purpose
reuptake inhibitors (SNRIs), Alpha-2 adrenergic antagonists, cannabinoids,
analgesics
lidocaine, capsaicin
TCA, SNRIs, anticonvulsant analgesics (gabapentin, pregabalin,
For neuropathic carbamazepine, lamotrigine, oxcarbazepine, valproate, topiramate,
pain levetiracetam, lacosamide, ) mexiletene, lidocaine, ketamine clonazepam,
baclofen
Bisphosphonates, calcitonin, radiopharmaceuticals (strontium-89, samarium-
For bone pain
153)
For bowel
Anticholinergics, somatostatin analogues, glucocorticoids
obstruction

NSAIDs are both anti-inflammatory and anti-pyretic and are used in cancer pain management.
NSAIDs are effective in inflammatory, visceral, bone, and neuropathic pain.39 Their main
mechanism of action is inhibiting prostaglandin synthesis via cyclooxygenase (COX) inhibition.
They are classified based on their ability to inhibit either COX-1 or COX-2 enzyme isoform.
COX-2 selective NSAIDs were primarily developed to reduce NSAID-induced gastrointestinal
toxicity, however, naming the "safest" NSAID is difficult as gastrotoxicity is related to multiple
factors. Other adverse effects related to NSAID use are increased thrombotic events, platelet
dysfunction, bleeding, bronchospasm, renal toxicity, and delayed bone healing.30

Adjuvant analgesics are drugs primarily marketed for conditions other than pain, but relieve
certain types of pain, either alone or when used in combination with a primary analgesic on each
step of the WHO analgesic ladder. Most adjuvants improve the therapeutic index of opioids but,
unlike opioids, have a ceiling effect, a narrow therapeutic window, and are less versatile in routes
of administration.40 Inferring the pathophysiology of the cancer pain syndrome guides adjuvant
analgesic choices. Based on their use in conventional practice, adjuvant analgesics are broadly
categorized as: 1) multi-purpose analgesics; 2) for neuropathic pain; 3) for bone pain; and 4) for
bowel obstruction.41 (Table 9)
Some cancer patients will not have acceptable pain control with systemic analgesic therapy and
will need additional approaches to pain control. Radiation therapy and interventional treatments
like neurolytic blockades, intrathecal drug therapy, kyphoplasty or vertebroplasty, or image-
guided tumor ablation may be useful when systemic medications fail to provide pain control or
when adverse effects become intolerable.42 Complementary therapies, such as guided imagery,
relaxation techniques, hypnosis, and biofeedback have also been used in the multidisciplinary
approach to cancer pain management.

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Outcomes

Relief of pain is generally measured by unidimensional or pain relief scales. Ancillary outcomes
include improved activities, relief of insomnia, improved mood and appetite. Patient satisfaction
with treatment, in addition to pain relief, reflects the relationship of the patient and the physician.
It is generally more difficult to see an improvement in overall quality of life because this is
influenced to a significant degree by the burden of multiple symptoms.

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Conclusion

Pain is one of the most feared symptoms associated with advanced cancer, but it also can be
effectively managed in the great majority of patients. A good pain assessment is vital to effective
treatment. Opioid therapy is the first-line approach in treating moderate to severe cancer pain.
Non-opioid analgesics and adjuvant analgesics improve pain control and should be used along
with opioids. In patients who do not get pain relief with systemic analgesic therapy,
interventional pain procedures and complementary therapies should be considered as part of a
multimodal cancer pain management.

Summary

 Cancer pain is broadly categorized as acute and chronic pain syndromes. Acute pain
syndromes are often iatrogenic but may also be disease-related. Chronic pain syndromes
are mostly due to direct effects of malignancy and some are due to antineoplastic
treatments.
 Clinicians should integrate findings from history, physical examination, and tests in order
to infer the pathophysiologic mechanisms behind the pain and identify the possible pain
etiology.
 Inferred pathophysiologies are nociceptive, neuropathic, or psychogenic. Disorders that
cannot be categorized are labeled idiopathic. Cancer pain is oftentimes a mixed disorder.
 Cancer pain can be relieved in 80% to 90% of patients using an opioid-based analgesic
regimen and the WHO analgesic ladder as guidelines.
 In patients who do not get pain relief with systemic analgesic therapy, interventional pain
procedures should be considered as part of multimodal approach to cancer pain
management.
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