Pain in Patients With Cancer
- Corresponding author: Pamela Goodwin, MD, University of Toronto, Mount Sinai Hospital, 1284-600 University Avenue, Toronto, ON, Canada M5G 1X5; e-mail:pgoodwin@mtsinai.on.ca.
Pain is an important concern in patients with cancer who are receiving active treatment and in long-term cancer survivors. It is one of the most feared aspects of cancer, and it can have a major adverse impact on quality of life. It has long been recognized that untreated or undertreated pain is common in patients with cancer, with little evidence of recent improvement.1,2 Given the many advances in knowledge regarding cancer pain and its management over the past decade, this Special Series issue was assembled to provide readers with an update on the current understanding of the biology of cancer pain, the biology and mechanisms of action of the opioids used to treat cancer pain, challenges in the management of cancer pain, and evidence-based multidisciplinary approaches to management of cancer pain. We hope that the articles in this Special Series issue will enhance clinician understanding of cancer pain and its treatment and provide practical approaches to managing pain in patients with cancer.
Hui and Bruera3 outline “A Personalized Approach to Assessing and Managing Pain in Patients With Cancer.” They provide a practical yet evidence-based approach to personalized pain assessment and management in the clinic. They also discuss a paradigm shift in pain management, outlining a multistep approach that includes systematic screening, comprehensive pain assessment, characterization of pain, identification of personal modulators of pain expression, documentation of personalized pain goals, and implementation of a multidisciplinary treatment plan with subsequent customized longitudinal monitoring. Their article summarizes an expert clinician's approach to pain management and provides practical tables and figures that will be helpful to the clinician who manages cancer pain.
Falk and Dickenson4 discuss the biology of pain in patients with cancer, with a special focus on bone pain, in their article entitled “Pain and Nociception: Mechanisms of Cancer-Induced Bone Pain.” The authors review mechanisms of cancer pain, stating that it is a “complex pain state involving components of both inflammatory and neuropathic pain, but also displaying elements that appear to be unique to cancer pain.” They discuss cancer pain as unpredictable, with highly variable intensity, which makes it difficult to manage. They also review mechanisms of acute pain, neuropathic pain, inflammatory pain, and complex cancer pain, providing informative figures that will help clinicians understand the biology of pain and may help guide the selection of management approaches.
Gavril Pasternak5 reviews “Opiate Pharmacology and Relief of Pain,” a complex area that is presented in a clear fashion. Pasternak states that opioids “selectively impact the hurt of nociceptive stimuli”; they act through activation of a pain modulating system consisting of endogenous opioid peptides and their receptors. He discusses three classes of opioid/receptors—mu, delta, and kappa—and suggests that individual responses to specific opioids may reflect differences in the biology of these receptors. Pasternak discusses important issues such as opioid cross tolerance, benefits, and risks of opioid rotation and the growing understanding of mu receptor subtypes, introducing the concept of “biased agonism.”
Portenoy and Ahmed6 discuss “Principles of Opioid Use in Cancer Pain.” They provide a practical approach to the use of opioids in patients with cancer and discuss available agents, including new agonists, partial agonists, and mixed-mechanism drugs. They discuss drug selection, route of administration, dose individualization, opioid rotation, and the management of breakthrough pain. They review management of adverse effects, as well as potential risks associated with nonadherence, opioid abuse, and diversion of drugs into the illicit marketplace. Their article includes a series of detailed tables describing opioid agents, equianalgesic doses, half-life, and duration of action, as well as guidelines for opioid rotation. This chapter is a must-read for practicing clinicians who prescribe opioids.
Mercadante, Porzio, and Gebbia7 discuss “New Opioids,” agents that have been recently marketed or are under development with characteristics that suggest that they will be useful in the management of cancer pain. One of the agents they discuss is tapentadol, a centrally acting oral analgesic that shows promise in the management of cancer pain. They also review combination agents (oxycodone-naloxone and buprenorphine-naloxone) that have been developed to reduce toxicity and minimize the potential for abuse. Finally, they discuss new delivery systems that will provide rapid onset of action for breakthrough pain. Many of the agents they discuss require additional research before they can be widely used in the clinic; however, it is important that clinicians be aware of the promise they show.
Vardy and Agar8 review “Nonopioid Drugs in the Treatment of Cancer Pain.” They discuss the use of anti-inflammatory agents, corticosteroids, antidepressant and anticonvulsant medications, bisphosphonates, and receptor activator of nuclear factor kappa B ligand inhibitors, critically reviewing the available evidence and providing guidance for the use of these agents in patients with cancer. Their detailed tables provide clinicians with important information regarding evidence of benefit, as well as potential mechanisms of action, toxicities, and interactions with other agents.
A series of three articles reviews the important contribution of nonpharmacologic interventions in the management of cancer pain. Cheville and Basford9 review “The Role of Rehabilitation Medicine and Physical Agents in the Treatment of Cancer-Associated Pain.” They describe the current standard for rehabilitation medicine care and discuss several approaches, including modulation of nociception (eg, use of heat and cold, electrical stimulation), stabilization and unloading strategies (eg, assistive devices for mobility, offloading of forces required to perform a painful activity, therapeutic exercise, orthotics, and positioning), use of modalities with physiologic effects that indirectly influence nociception (light, laser therapy), manual lymphatic drainage and, finally, rehabilitation approaches to managing musculoskeletal pain, including the combination of rest, ice, compression, and elevation (commonly called RICE), deep heat, injections, myofascial release, massage, and exercise. Recognizing the limitations of some of the available evidence, they provide a framework for use of these modalities in cancer pain management. Syrjala et al10discuss “Psychological and Behavioral Approaches to Cancer Pain Management,” highlighting the role that psychological factors (emotional distress, depression, anxiety, uncertainty, hopelessness) can have on the experience of pain. They outline psychological and cognitive behavioral treatments, including coping skills training, hypnosis, cognitive behavioral approaches, and relaxation with imagery, that have been shown to reduce pain severity in high-quality randomized trials. They also discuss approaches such as yoga and exercise that have a lower level of evidence of benefit. They advocate for multidisciplinary teams that include expertise in psychological and behavioral interventions in the management of cancer pain. In the final article in this group, Lovell et al11 discuss “Patient Education, Coaching, and Self-Management for Cancer Pain: A Review of the Evidence and Translation to Practice.” They synthesize available evidence to identify elements of patient education that are effective in reducing pain and pain interference, including question prompt lists, pain diaries, checklists, and personalized pain management plans. They highlight the need for education in patients with low health literacy and provide links to available tools that may be helpful in managing cancer pain. They also highlight the importance of patient centeredness in providing education and recognize that patient education is dynamic and interactive rather than static and passive. Like many other authors, they advocate for interdisciplinary partnerships with patients to optimize cancer pain management.
Another series of three articles addresses common challenges in cancer pain management. Paice and Von Roenn12 discuss the “Under- or Overtreatment of Pain in the Patient With Cancer: How to Achieve Proper Balance.” They highlight the fact that up to 50% of patients with cancer have undertreated pain, identifying age older than 65 years, minority status, misconceptions about analgesics and their adverse effects, as well as physician knowledge deficits and inadequate pain assessment practices as being risk factors for undertreatment. They briefly discuss overtreatment, highlighting that little data exist in the cancer setting, and they discuss potential long-term adverse effects, including difficulty concentrating, sedation, hypogonadism, and opioid misuse or addiction. They discuss the potential for weaning patients from opioids when overtreatment is suspected. Kwon13 reviews “Overcoming Barriers in Cancer Pain Management.” Key barriers relate to health care professionals (poor pain assessment, lack of knowledge and skill, reluctance to prescribe opioids), patients (cognitive factors, affective factors, and adherence), as well as the health care system (regulatory limits on access to opioids, limited availability of pain and palliative care specialists). Interventions to address professional and patient barriers to pain management are discussed, and strategies to overcome barriers are outlined. Finally, Del Fabbro14 reviews “Assessment and Management of Chemical Coping in Patients With Cancer.” He refers to a working definition of chemical coping as “the intake of opioids on a scale that spans the range between normal nonaddictive opioid use for pain all the way to total addiction and its accompanying compulsive, destructive behavior.” The prevalence of chemical coping in patients with cancer is unclear; however, those with a history of alcoholism are at greatest risk, and those approaching the addiction end of the chemical coping spectrum are at increased risk of morbidity and mortality. The authors introduce the CAGE questionnaire, a four-item validated tool that screens for chemical coping, and they discuss approaches to management of chemical coping in patients with cancer, recognizing that there is a need for additional research in this area.
The final article by Glare et al15 discusses the complex issue of pain in cancer survivors. This group of patients is highlighted here because of their growing number and the potential for long-term pain after initial cancer treatment. Glare et al review the epidemiology of pain in cancer survivors, contributing factors, and approaches to management, including pharmacologic agents, exercise, and cognitive behavioral strategies, as well as physical medicine/rehabilitation, and integrative medicine (acupuncture and massage) interventions. They emphasize the need for a multidisciplinary team approach.
Many themes emerge in the articles included in this Special Series issue. First, pain is common in patients with cancer and survivors, it is often undertreated, and it can lead to significant distress. Several effective approaches to management are available, including opioids, but it must be recognized that the use of a multidisciplinary approach with the introduction of nonpharmacologic interventions, including education, psychosocial support, and physical therapies, is critical for optimal pain management. Challenges to cancer pain management include the need to find a balance between patient-centered over- and undertreatment of pain, the need to deal with recognized barriers to pain management (at patient, physician, and health care system levels), and the emerging recognition of the potential for abuse and diversion of opioids prescribed for cancer pain. It is our hope that the information included in this Special Series issue provides a state-of-the-art review of the current understanding of pain biology and treatment that will be useful at a practical level for clinicians involved in the management of cancer pain.
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