Given the lack of agreement over the definition of BtCP, its epidemiology is similarly ill defined. Portenoy and Hagen’s original description of BtCP cited a 64 % prevalence of breakthrough pain among patients with cancer. A more recent international survey of pain specialists reported a similar prevalence of 64.8 % [9]. The most recent systematic review by Deandrea et al. reports a pooled prevalence estimate of 59.2 %, with a significant amount of variability depending on the site [10]. For example, the pooled prevalence estimate reported by Deandrea and colleagues was noted to be much lower in outpatient clinic settings (39.9 %) and much higher in hospice (80.5 %). Caraceni and coworkers conducted a study of BtCP that required educational sessions with palliative care clinicians to ensure all were using common diagnostic criteria for BtCP; they found a prevalence of 73 % [8]. Other evidence suggests, however, that despite the high prevalence of BtCP, this condition remains under-recognized and thus undertreated [11].

Longitudinal study has shed further light on the experience of patients facing BtCP in daily life [12]. Mercadente and colleagues followed 101 consecutive cancer patients admitted to a home palliative care program in Italy [12]. At baseline, 70.2 % of patients were receiving analgesics and 52 % had uncontrolled pain. Just over 49 % reported a mean number of 2.4 episodes of BtCP per day and an average pain duration of 35 min per episode. Among these, two-thirds had pain with movement; ceasing the movement decreased pain spontaneously in 74 % of the patients with movement-related pain. Over three-quarters (78 %) of these patients noted marked limitation in physical activity due to their pain. Interestingly, most of these patients did not have a prescription for a BtCP medication at time of admission to the home palliative care program. At the time of the second assessment 1 month later, more patients had been started on a BtCP medication, and the incidence of breakthrough pain with movement had decreased significantly. These findings suggest that poor awareness of BtCP as a clinical entity remains a major problem and that BtCP significantly limits the activity level of patients. These results also suggest, however, that medications aimed at addressing BtCP may improve patients’ mobility.

BtCP also appears to be particularly prevalent in the hospice setting. One detailed longitudinal study of 22 hospice patients found that 86 % experienced an average number of 2.9 episodes of breakthrough pain per day with an average intensity of 7 on a 10-point scale [13]. The average baseline pain scores for these patients were 3.6 during the day and 2.6 at night, suggesting quite good pain control at baseline, but clearly they also experienced episodes of significant, severe breakthrough pain. Episodes of breakthrough pain lasted 52 min on average, and the average time to relief was upward of 30 min. Interestingly, caregivers’ perceptions of the severity, duration, amount of relief, and time to relief were very inaccurate and were generally underestimated.

Despite the lack of a consensus on the definition of BtCP, its descriptions in the published literature include several important features worth highlighting. First, BtCP can have a significant negative impact on a patient’s quality of life and can be present at any stage of disease [14]. In one longitudinal study of patients with and without cancer, investigators assessed the impact of breakthrough pain on ambulatory patient’s health-related quality of life [15]. Breakthrough pain was associated with increased somatic complaints in this study. Patients also reported their pain posed significant interference with their function. Other evidence similarly demonstrates that BtCP has negative impacts on patients’ mobility [16]. Beyond this, BtCP patients are dissatisfied with both the impact that pain has on their lives and with their pain management in general [17].

BtCP is often described in different categories, either relating to its likely etiology or along more anatomic and pathophysiologic lines. As briefly presented earlier (Table 8.2), Payne describes the three main categories: (1) incident, (2) end-of-dose failure, and (3) idiopathic. The so-called incident pain occurs in relation to a specific activity or event. For example, patients may develop incident pain each time they attempt to change position or get up from a chair. Others may experience incident pain upon turning a certain direction or walking briskly instead of slowly. Still others might experience incident pain with certain stimuli, such as cold temperature or fabric touching an affected area of the skin. Whether the pain is physiologic or neuropathic in origin, it is useful to categorize the resulting pain as “incident.” This is because the predictable occurrence of pain in certain settings allows patients to anticipate the pain and to take premedication before doing an expectedly offending activity or to modify their activity to reduce the occurrence of pain.

Idiopathic breakthrough pain, on the other hand, is not predictable. For example, a patient might suffer significant intermittent, cramping abdominal pain. There may not be a clear trigger, though it is important to undertake efforts to identify a less obvious one, which could lead to suggestions about ways to minimize or avoid the pain. In the case of idiopathic BtCP, one cannot readily premedicate or alter routine behavior to improve the pain. Instead, other approaches are necessary, as discussed later below.

End-of-dose failure is a very common and distinct type of breakthrough pain. This occurs when a patient’s existing analgesic medication “wears off” toward the end of the dosing interval. For example, a patient may take long-acting morphine sulfate every 12 h but begin experiencing an escalation of pain about 10 h after each dose. In this case, it is not necessarily any particular activity or underlying pathophysiology that is leading to the breakthrough pain, but rather the kinetics of how the opioid behaves in this particular patient. Adjustments to the dosing interval or amount can be highly effective once adequately titrated.

Considering the three aforementioned types of BtCP clearly has important implications for management strategies, given their very different underlying etiologies. Similarly, considering the pathophysiologic etiology of BtCP can also be effective at informing a plan to effectively address it. Pain is often categorized within four main categories: (1) somatic, (2) visceral, (3) neuropathic, or (4) mixed. Somatic and visceral are types of nociceptive pain. Somatic nociceptive pain generally involves injury to structures, such as bones or muscles. Patients classically describe somatic pain as “aching,” “throbbing,” or “pressure-like” in its quality. Visceral nociceptive pain is due to injury of a viscus. This could involve a more “cramping” pain in the context of hollow viscus obstruction, as in the case of a malignant bowel obstruction, or perhaps more “gnawing” pain from capsular stretch of the liver or other such organs. Neuropathic pain, on the other hand, is generally due to damage to the nerves themselves. It thus manifests quite differently than nociceptive pain, instead often described like an “electric shock,” or “burning,” or even as an excessive sensitivity to normal stimuli (often referred to as “allodynia”). So-called mixed pain, as its name implies, is due to multiple etiologies. For example, a patient may experience both somatic and neuropathic pain in the context of a bony tumor that causes nerve infiltration or compression.

While there is no universal agreement on the categories and types of BtCP, it is useful to consider a similar framework when evaluating a patient with unresolved pain. The three general categories (incident, idiopathic, end-of-dose) can help suggest a useful management approach, while the main pathophysiologic categories (somatic, visceral, neuropathic, mixed) can point toward additional key considerations regarding the use of adjunctive analgesics or even interventional procedures that will lead to more optimal palliation of the most bothersome symptoms.