Classification of Cancer Pain Syndromes

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 specialists.[15-17]

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 pain.[21]

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 mood.[22]

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 identify.

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).

Controversies

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]