Introduction

Pain is one of the most common and distressing symptoms among cancer patients, with increasing frequency and severity as disease progresses. Approximately 30–50% of newly diagnosed cancer patients report having pain. This proportion increases to 35–96% in terminally ill cancer patients [1]. Despite significant progress in research and education on pain management, there remain multiple barriers to effective pain control. These include inconsistent pain assessment, insufficient training and knowledge, misconceptions about opioids and financial challenges [2]. In addition to overcoming these obstacles, it is important to recognize that the diagnosis of cancer is associated with significant physical, psychological and spiritual distress, all of which can contribute to worsening pain. Thus, effective management of cancer pain necessitates an interprofessional approach customized to the individual’s needs.

Basic mechanisms

Patients with cancer may experience pain from progressive disease, diagnostic procedures, cancer treatments and/or other comorbidities. Table 38.1 provides an overview of cancer pain mechanisms. The basic mechanism of nociception is reviewed in Chapter 3 and is not discussed in this chapter. Cancer is a life‐threatening disease and is frequently associated with psychosocial distress. Although the pathway of neurotransmission from noxious stimuli to somatosensory cortex is similar between cancer pain and non‐cancer pain, how cancer patients perceive, and ultimately express, their pain may be quite different from patients with non‐cancer Diagnoses (Figure 38.1).

An understanding of the unique circumstances associated with the diagnosis of cancer has important implications for both assessment and treatment of cancer pain. Cancer patients typically have a heavy symptom burden as a result of progressive cancer, cancer treatments and/or comorbidities. Using the Memorial Symptom Assessment Scale, one study demonstrated that advanced cancer patients have an average of 11 ± 6 symptoms [3]. Because many of these symptoms are closely related, effective management of pain in the context of malignancy requires concurrent management of other complaints (e.g. coughing and chest pain, vomiting and abdominal pain). Also, polypharmacy is a common issue among cancer patients, with a high potential for drug interactions. For instance, the level of methadone may be affected by concurrent use of various CYP3A4 inducers and/or inhibitors.

Clinicians caring for cancer patients should be cognizant of the concept of “total pain,” defined as the sum of four components: physical, psychological, social and spiritual. This framework highlights the complex interconnectedness between the body, mind and spirit. For instance, a patient may experience 4 out of 10 shoulder pain caused by the nociceptive input from bone metastasis, while another patient with similar level of noxious physical stimuli may rate his/her pain as 10 out of 10 because of significant psychosocial (e.g. recent bad news) or spiritual (e.g. punishment from God) distress. Pain for the first patient can easily be managed with analgesics, while pain for the second patient warrants comprehensive assessment with multidisciplinary input.

Poorly controlled pain can result in reduced sleep, decreased function, altered mood and can significantly compromise a patients’ quality of life. When a patient requires ever‐increasing doses of analgesics without adequate pain control, it is important to step back and look for specific risk factors (Table 38.2) before prescribing more medications. This not only helps to minimize the amount of analgesics and thus the associated side effects, but also provides a more effective pain control strategy.

Assessment

Effective management of cancer pain begins with regular and frequent screening, which allows clinicians to diagnose pain early, to initiate treatment in a timely fashion and to monitor the effectiveness of therapy.

In addition to a focused pain history and physical examination, it is critical to assess common factors that may affect pain management. At our center, we routinely screen patients for various physical and psychological symptoms, delirium and history of alcoholism, using validated instruments such as the Edmonton Symptom Assessment Scale (ESAS; Figure 38.3) [4], the Memorial Delirium Assessment Scale (MDAS) [5] and the CAGE questionnaire [6], respectively. This information can help clinicians formulate the pain diagnosis and assess the need to utilize specific pain management strategies. For instance, a delirious patient who keeps complaining of pain should be treated with neuroleptics rather than simply escalating the opioid dose. In another example, a patient with 10 out of 10 pain and severe symptoms in multiple other ESAS domains is likely to have a psychosocial component contributing to the overall experience of pain and would benefit from further psychological assessments.

Recognizing the importance of these factors, the Edmonton Classification System for Cancer Pain (ECS‐CP) is a pain assessment tool that has been validated in predicting pain management complexity [7]. It consists of five clinical factors: pain mechanisms, incident pain, psychological distress, addictive behavior and cognitive impairment, as outlined below (Figure 38.2) [8]. Involvement of one of more of these complexities in a patient’s pain picture has been shown to influence multiple factors including the time, MEDD and number of adjuvant analgesics required to achieve pain control [9]. One important note is that it doesn’t take into account addictive behavior if it occurred remotely. Because people tend to employ the same coping mechanisms when dealing with stress, a history of alcoholism any time in the past should be relevant [10–12]. Regular assessment and documentation using ECS‐CP will facilitate communication between members of the interprofessional team and help optimize pain control.

Management

In 2018, the World Health Organization updated its guidelines to say that it is appropriate to initiate a pain regimen with opioids in the context of moderate to severe cancer‐related pain, alone or in combination with non‐steroidal anti‐inflammatory drugs (NSAIDs) and/or acetaminophen. This is a change from their previous recommendation to initiate all patients on non‐opioid therapies, regardless of their pain level. However, this should be done on a case‐by‐case basis and other factors, such as risk of non‐medical opioid use, should be taken into account (to be discussed later). Adjuvant treatments such as antidepressants, anticonvulsants, bisphosphonates, steroids, radiation and chemotherapy may be added to the pain regimen at any time if indicated.

Opioid mechanism of action

Details of opioid action have been reviewed in Chapter 19. Opioids exert their analgesic effect through binding to various μ‐, δ‐ and κ‐receptors, both centrally and peripherally. Activation of μ1‐receptors is responsible for the analgesic and euphoric effects of the opioid, while interaction with μ2‐receptors is associated with various opioid‐induced side effects such as respiratory depression, nausea and sedation. Methadone also has N‐methyl‐D‐aspartate (NMDA) antagonist activity, which is associated with a theoretical benefit for neuropathic pain and opioid resistance.

There is great interindividual variation in the degree of responsiveness to opioids, which is dependent on various pharmacodynamic and pharmacokinetic factors. These in turn are affected by the patient’s age, sex, genetic makeup (i.e. opioid receptor expression and sensitivity, P450 enzymes), organ function, comorbidities, diet and concurrent medications. For instance, 8–10% of the Caucasian population have an inactive CYP2D6 variant and cannot convert codeine from its prodrug form to the active metabolite. The pharmacogenomics of opioid agents represents an area of active research.

Because pain expression is a subjective measure, psychosocial factors such as personality, past experience, culture and placebo effect may also affect the response.

Clinical use of opioids

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