Classification of Cancer Pain Syndromes

Classification of Cancer Pain Syndromes

ABSTRACT: Cancer patients experience pain in multiple sites and from several pathophysiologies of the symptom complex. The fluctuating nature of cancer pain intensity is a relevant clinical feature and depends on disease patterns and pain mechanisms. Breakthrough pain is defined as episodes of pain that "break through" the control of an otherwise effective analgesic therapy. Traditional ways of classifying pain in the cancer population include distinguishing pain associated with the treatments, the tumor, or unrelated to both and between chronic and acute pain. In focusing on the care of the cancer patient with pain, it is useful to be familiar with the characteristics of the typical syndrome found in association with different tumor types and anatomic locations. An understanding of the etiology of pain in relation to the cancer is useful in recognizing these complications and in treating them. This article reviews the methods presently applied to the classification of cancer pain and highlights the need for more research in this area. [ONCOLOGY 15:1627-1647, 2001

The terms "cancer pain" and
"cancer-related pain" distinguish pain in cancer patients from pain in
patients without malignancies, but they do not convey details of the
characteristics, etiology, and pathophysiology of pain. Cancer patients may
experience many different types of pain. This fact was recognized decades ago,
and systematic assessment of cancer pain syndromes has evolved since the
pioneering work of Kathleen Foley, who first described the complex phenomenology
of cancer pain in the 1970s.[1,2] Another important early description of cancer
pain came from the hospice experience in the United Kingdom.[3] After these
initial empiric efforts, the definition of pain associated with cancer was
refined as schemes by Foley and Twycross were perfected with more detailed lists
of significant clinico-anatomic entities. These updated lists were derived from
the experience of different authors from several centers.[4-7]

It was already evident from the earliest reports that the prevalence of pain
among cancer patients was high, and that cancer pain may result from
antineoplastic treatments or the tumor itself. It is now recognized that cancer
patients experience pain in multiple sites and from several pathophysiologies of
the symptom complex.

The importance of classifying cancer pain syndromes depends on the goal of
the clinical or research task for which the classification is to be used. Cancer
pain classification schemes may be temporal, etiologic, anatomic,
pathophysiologic, or syndromic.

Pain Assessment and Clinical Presentations

Pain History

A pain history must be comprehensive and elicited directly from the patient,
whenever possible. In particular, questions about pain location, radiation,
referral, quality, intensity, duration, and temporal variation, as well as
provocative and palliative factors, must be noted. The PQRST mnemonic is quite
useful in the clinical setting: P = provocative/palliative factors; Q = quality;
R = region, radiation, referral; S = severity, using intensity rating scales; T
= temporal features.[8]

Number of Pain Sites

The location and number of pain sites are often formally recorded by the
patient or clinician on body charts. This information is also included in many
pain assessment tools.[9,10] Multiple sites of pain are common, especially when
pain is related to metastatic disease. The number of different pains reported
varies considerably, but most authors agree that between 70% and 80% of cancer
patients have pain from two anatomically distinct sites.[3,11] One report
recognized more specifically the presence of two or more distinct pain syndromes
in 70% of cases.[11] Differences in assessment methods can be a source of
significant variability in the descriptions of pain syndromes.

Temporal Variation

After a pain history is taken and the location of the pain described, the
next fundamental clinical characteristic to be assessed is pain intensity.[12]
Pain intensity is assessed by validated subjective ratings using visual analog
scales, numeric or verbal rating scales, or pain questionnaires.[10,13,14]
Intensity is often the main feature of pain guiding therapeutic interventions.
The fluctuating nature of cancer pain intensity is a relevant clinical feature
and depends on disease patterns and pain mechanisms. The occurrence of
significant episodes of pain that "break through" the control of an
otherwise effective analgesic therapy led to the definition of breakthrough
pain. This term is used primarily by North American cancer pain

Definition of Breakthrough Pain

Portenoy and colleagues have defined breakthrough pain as "a transitory
exacerbation of pain that occurs on a background of otherwise stable pain in a
patient receiving chronic opioid therapy." There are three important
aspects of this phenomenon:

  1. Intensity—Breakthrough pain manifests as an increase in pain intensity.
    To be clinically meaningful, a certain intensity level has to be set as a
    threshold, ie, a level that would prompt changes in therapy. This severity
    threshold can change. Pain described as greater than moderate-to-severe or
    excruciating was the level used in the original definition.[15] On a numeric
    (0 to 10) rating scale, most breakthrough pain requiring treatment was
    rated of 5 or more.[18] In accordance with these definitions, treatment strategies
    for breakthrough pain have been investigated.[19,20]
  2. Temporal Factors—Breakthrough pain is by definition transitory, to be
    distinguished from an increase in the intensity of background pain. To be
    considered transitory, the pain episode has to be linked to a reversible
    provocative factor (eg, movement) or be terminated by analgesic measures.
  3. Therapy—The third concept links breakthrough pain with an established
    ongoing analgesic regimen usually based on opioid administration. Pain,
    therefore, breaks through the analgesia provided by regularly administered
    medications. This characteristic limits the concept and, in subsequent
    definitions, has been eliminated to give a more general meaning to breakthrough

Epidemiology and Clinical Implications

Between 40% and 80% of cancer pain patients experience breakthrough
pain.[15,18,22-24] We can conservatively estimate a prevalence of 65%.[22,24] In
one survey, breakthrough pain was independently associated with more severe pain
intensity on multivariate analyses.[24] Another study confirmed that
breakthrough pain has a negative effect on quality of life, function, and

One important aspect of the management of breakthrough pain is the
identification of precipitating factors. Some breakthrough pains are
precipitated by volitional actions (movement, posture, and touch), and in such
cases, breakthrough pain is synonymous with incident pain.[15,18,22]
Breakthrough pain may also occur spontaneously as a result of some automatic,
involuntary action (visceral reflexes such as bowel spasm, ureteral distension,
or swallowing). Breakthrough pain can otherwise be spontaneous or the result of
therapeutic failure, such as pain worsening at the end of analgesic efficacy. In
the clinical setting, the causes of some breakthrough pain are difficult to

The pathophysiology of breakthrough pain has been poorly studied. In one
International Association for the Study of Pain (IASP) Task Force study, the
presence of breakthrough pain was strongly associated with bone pain syndromes,
especially vertebral bone pain (87%), and with pain due to plexopathies (78%)—suggesting
the existence of breakthrough pain with different mechanisms and
pathophysiologies (personal communication, Caraceni and Portenoy, 2001).


Although breakthrough pain is considered an important aspect of cancer pain,
its diagnosis and definition is controversial. Different definitions are
possible, ranging from general to specific (as discussed above), depending on
intensity, duration, relationship to the therapeutic regimen, precipitating
factors, and so on. When the concept has been used in other than an Anglo-Saxon
cultural setting, the wide variation in interpretation suggests cultural
differences will have to be better appreciated before the concept can be
universally applied.[24]


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